HIV-1

CAEV vs HIV: But what if it could, tho?

sa smith — Sat, 06 Feb 2016 16:52:31 +0000

CAEV vs HIV: But what if it could, tho?

Listen, nobody thinks the guy who 'cured Charlie Sheen of HIV' cured Charlie Sheen of HIV.

Even Charlie Sheen.

Dr Sam
I was with u in
Mexico for
1 day.
It's illegal for u
to practice in
U.S.A. where u
treated me for 2 months
© https://t.co/lKv6YPYdhm

— Charlie Sheen (@charliesheen) February 1, 2016

... But what if he could, tho?

What would this super awesome therapy THE MAN doesnt want you to know about look like? How would it work?

That would be a fun and educational game to play!

Okay, to play this game you first have to understand what 'CAEV' is. Caprine arthritis-encephalitis virus is a retrovirus that infects goats. It is 'like' HIV in the sense that they are both lentiviruses, that is, more complex (more genes) retroviruses. They both share the standard gag, pol, and env genes all retroviruses have, plus a few accessory genes: rev, tat, and vif. HIV also has a few more.

But while there are similarities, CAEV and HIV are not 'the same' any more than you and blue whales are 'the same' (I tried to align an amino acid sequence of a CAEV Env with an HIV-1 Env, and the program was like 'Nuh uh. Dees dont go together.')

So: How could CAEV be used to cure HIV?

1-- Anti-CAEV antibodies from goats could stop HIV!

Dr. Whatever said, specifically, that he 'looked for the absence of disease'. Where should there have been HIV, but there wasnt, and figure out what was different in the environment. His finding? The people drank milk from arthritic goats (CAEV infected animals), and were 'cured' of their HIV infections.

Maybe it was the anti-CAEV antibodies secreted in the goats milk that stopped HIV?

Not likely.

First, adult humans, like Charlie Sheen, like the HIV free people in this community, dont absorb antibodies from the foods we eat. We certainly could not absorb concentrations of antibodies necessary to stop the number of viruses circulating in humans during acute or substantially progressed HIV infection.

Even if we did, the process would eventually stop working.

Why?

Because we would eventually start making antibodies to the goat antibodies.

They are not something your immune system would recognize as 'self', so your body would try to stop these foreign proteins, even if the antibodies were 'helping'. Your immune system doesnt know or understand that.

That is why when we make antibodies for therapy, they must be genetically modified to look as 'human' as possible.

This is also granting the premise that the goat antibodies would stop HIV, which looks significantly different from CAEV... when they aint stopping CAEV in the goat.

There is some evidence that some goat antibodies can 'see' parts of HIV. But 'seeing' HIV and 'stopping' HIV are entirely different things. People infected with HIV make LOTS of antibodies that 'see' HIV... but they dont do jack shit to stop the virus.

That is the kicker, and there is no evidence that goat CAEV viruses can neutralize HIV, or mediate ADCC activity, or stop HIV in any capacity.

2-- CAEV for HIV is like cowpox for smallpox!

Dr. Whatshisface also mentioned cowpox/smallpox. MAYBE it isnt the antibodies in goats milk that are stopping HIV, but the actual virus!

If the virus is being transmitted to humans via milk, and these humans are making their own antibodies that stop CAEV which cross-react with HIV, then that gets around the humanized antibody therapy thing, right?

Maybe!

... But then again, this still doesnt address the fact that antibodies to CAEV would not necessarily translate into antibodies that can stop HIV. I mean, just to reemphasize this point-- You know how you have to get a flu shot every year because the flu changes? And the antibodies you made that protected you last year might not protect you this year? Little changes between variants of influenza drastically effect your immune systems ability to stop the virus. This strategy bets that two different species of retroviruses, viruses whos *specialty* is evading antibodies, cross-react beautifully to stop disease.

I would not make that bet.

And then there is no evidence humans are exposed to CAEV via goat milk and make protective anti-HIV antibodies. Indeed, if this were the case, these 'protected' individuals would 'test positive' for HIV. Initial HIV tests look for antibodies to HIV... so the test would would detect the cross-reactive antibodies in these 'CAEV' people. They would all be HIV positive, and have no viral loads (because they were protected from HIV). And then the scientific community, not some random dude, would be studying these populations to figure out 'how they were controlling HIV'. *shrug*

3-- CAEV as a gene-therapy vector vs HIV!

To his credit, Dr. Dude did say that his magic approach to curing HIV was not like what scientists were doing-- genetically modifying viruses to cure cancers and genetic diseases.

But, since hes not really doing anything and we are just playing, lets pretend. Maybe CAEV could be used as a gene-therapy vector to stop HIV!

This could work, maybe!

Lentiviruses are relatively safe ways to deliver 'healthy' genes. And humans, just walking around, probably are not making antibodies to CAEV (they are so some of the preferred vectors, causing problems). But we have no idea what cells, if any, CAEV would infect-->deliver genes in humans. We dont know how well CAEV would express the delivered genes. We also dont know what information to give CAEV. CRISPR to cut out CCR5? The genes for producing broadly neutralizing antibodies?

I am not sure this is a promising avenue of research (CAEV as gene therapy, not gene therapy vs HIV in general)-- I could only find one publication on this topic in PubMed, and its from 2006.

Dear Mr. Maher--

Ill be on the West coast in a couple weeks if you want to have a real Dr. on your show to talk about HIV.

Have your people call my people.

--ERV

sa smith Sat, 02/06/2016 - 11:52

Tags

Pop Culture

retrovirus

science outreach

Skepticism/Critical Thinking

virology

HIV-1

this subject is controversial thus need more extensive research but to make insinuations to the contrary does not prove or disprove anything. scientist/doctors disagree on many things so making comments and correlate studies with a bunch of maybes as a conclusions does not prove a point.

this subject is controversial thus need more extensive research
No, people saying "Bullshit!!!" is not the same as "needs more extensive research".
But if you want to pay for that research, go for it!

I ate bacon for breakfast this morning. I did not catch the flu today. Maybe swine flu protected me from human flu? Should we spend a few $million studying this? Should you pay me a few $thousand to eat some bacon I cooked up in Mexico?

I mean, I guess if you're looking for new novel vectors CAEV isn't the worst choice. It's a virus that infects mammals (good) and most humans haven't already been exposed to and therefore don't already have immunity to (good). But the non-human part is also bad because the virus might not infect people at all, or only poorly, or only the wrong kind of cells.

So I'm pretty sure there are more systematic ways of finding new lentivirus vectors than what a known crazy celebrity's not-doctor says.

I read a vox article that made a pretty strong claim about human milk.

http://www.vox.com/2014/5/10/5699674/6-remarkable-things-science-has-ta…

From the article:

Worldwide, only about 10 to 20 percent of infants breastfed by mothers with HIV catch the virus, and new research has identified the reason. A protein called Tenascin-C, naturally present in all breast milk, binds to the virus and prevents it from attacking human cells.

Is this woo or an up and coming treatment? COULD it be a treatment?

HIV and Charlie Sheen

sa smith — Tue, 17 Nov 2015 08:05:40 +0000

HIV and Charlie Sheen

ERV-->TMZ?

No, this is an education and outreach opportunity, and I want to use it to the best of my ability as an HIV researcher.

1-- I am so glad Charlie Sheen got tested for HIV. Most people who should be, dont, because even faced with a treatable, deadly disease, denial is *incredibly* attractive. 'If I dont know, then it cant be real' is a tall hurdle *many* of us will have to clear for some reason, at some point in our lives. Sheen got tested, and that is the first step to stopping HIV.

2-- "I have to... I have to. I am here to admit, in fact, I am HIV positive."

*wince*

'Coming out' is obviously very difficult for Sheen, and not something he felt comfortable doing. Sheen was forced out-- I have also heard rumors he was paying people to keep this information private. Complete and utter bullshit. Sheen doesnt owe the general public knowledge about his medical heath. It is fine if someone wants to be a celebrity voice for <insert any disease/cause/whatever>, but someones HIV status is literally no one elses business except the people they are having sex with.

Forcing someone out like this, in 2015, is deplorable.

3-- There has been some suggestion that the 'reason' people forced him out, was that Sheen was not open with all of his sexual partners. Sheen says "... threatening the health of so many others, which couldnt be farther from the truth." But both statements could be true. HIV+ individuals on antiretroviral therapy, who have low/undetectable viral loads, who use condoms, their partners are at low risk of becoming infected. But it is the *partners* decision whether the risk, however negligible, is acceptable. Not telling someone, and making the executive decision about risk for them, is 100% unacceptable. While there is argument over whether this should be criminal, or not, I am of the opinion that if you are HIV positive, it is not your decision to declare your partner is not at risk. Educate yourself, educate your partner, and make these decisions together.

I cant believe after all the progress society has made on HIV/AIDS in the past few decades celebrities have to 'admit' they have HIV to Matt Lauer.

Use condoms. Get tested. Educate yourself. Educate your partner. Encourage your politicians to get everyone who is HIV+ access to proper medications. And unless you are sleeping with a celebrity, their HIV status is none of your damn business.

sa smith Tue, 11/17/2015 - 03:05

Tags

HIV/AIDS

Pop Culture

HIV-1

Also: use clean needles, be very picky about your tattoo artist and piercers, try to avoid being in an altered mental stated while engaging in any of the listed activities.

I'm not interested in celebrities medical information (or really any information), but I hope that for people who are interested in celebrities, this creates opportunities for conversations about safe sex and HIV.

Hi Abbie, Do you have an email address. I have a few questions.
Enjoy your blog, as always.

Yup! Im terrible about getting to emails these days, but its endogenousretrovirus at gmail :)

A pandemic worse than HIV is coursing though the population. A retrovirus being pumped through the vaccine needles of unsuspecting population. And only Mikovits has discovered the true nature of this pandemic an hgrv, mlv retrovirus. The biggest cover-up of all.

http://powerpointparadise.com/blog/2015/12/25798/

You DO know how crazy you sound there, right?

"HIV+ individuals on antiretroviral therapy, who have low/undetectable viral loads, who use condoms, their partners are at low risk of becoming infected."

How come? What is the risk?

Unimpressive political stunt: HIV research fraud behind bars

sa smith — Tue, 07 Jul 2015 17:06:03 +0000

Unimpressive political stunt: HIV research fraud behind bars

So the guy who faked some HIV research results is officially going to spend about five years in jail, and has to pay back $7 million.

Former ISU scientist's stiff fraud sentence sends message

Yeah. It does send a message. The message is "The US government is not going to really investigate any of this, but every now and then we are going to go after some random nobody 'to send a message'".

My opinion on this topic has not changed in a year.

Oh! Thank god someone finally did something about that tyrant assistant professor from Iowa who fucked up, got caught, admitted what he did, and showed remorse. THANK GOOOOOD.

Thank GOD no one wasted their time investigating someone who worked for a major US research organization with his wife and 'career' underlings for ~35 years, got caught 'artistically' presenting results in a major scientific publication, never acknowledged any wrongdoing, showed no remorse, wasted millions upon millions of dollars and research man-hours, created panic in the general public. Thank GOD he got to 'retire' without any investigation into whether any of this other publications were also 'artistic', bending numerous fields of research down wrong paths.

No, thank GOD they got the assistant professor. From Iowa.

*smokecalmlywaifsoutERVsears*

Whatever.

Look, Han is an ass. Dirty piece of shit for faking data. He deserves to be punished.

But his 'punishment' is a dance-number to hide the fact 1) more of this kind of shit needs to be investigated, and 2) there are a *lot* bigger fish out there that need to be fried. Who werent. Inexplicably.

While I certainly fear taking research fraud more seriously could be exploited for personal/political gain (wasting time/resources if disgruntled ex-employees or competitors ledge false accusations against researchers), I do believe there is a happy-medium that can be reached between this, and the current state of doing virtually nothing when intent to deceive and defraud the research community is blatantly obvious.

sa smith Tue, 07/07/2015 - 13:06

Tags

General Science

HIV/AIDS

HIV-1

This was Grassley's doing;* ORI gave him the standard three-year ban.

Once Grassley pressured DOJ – in the form of Nicholas Klinefeldt – into action, Han lacked the sophistication to do more than naively hope for the best from the justice system.

He shouldn't have returned from South Korea without a better deal in place, IMHO.

* With the administration's acquiescence, apparently.

'Functional Cure for HIV' sounds like it would be better as a 'HIV vaccine'

sa smith — Wed, 08 Apr 2015 17:49:21 +0000

'Functional Cure for HIV' sounds like it would be better as a 'HIV vaccine'

You all know me.

There are two things I really love:

Studying HIV
Using viruses for gene therapy

One would think I would be over-the-moon about the FDA approving human trials for a gene therapy to stop HIV. HIV! Gene therapy! YAY!!

With HIV Cure as the Goal, Gene Therapy Research Expands

When this line of research initially emerged, I WAS super excited:

GMO in GMOs used to make GMO cells to treat HIV

Go read that.

Now, just to be clear, that was in no way a 'functional cure'. No one in that small trial was 'functionally cured'. But I still thought it was a great, creative step in a positive direction:

4– No way this is a viable world-wide ‘cure for HIV/AIDS’. But it is more viable than bone marrow transplants, and optimizing this protocol could get it cheaper/faster/safer for the developing world, aka, the place we really need a cure for HIV/AIDS.

But this is really cool. Really cool step in a positive direction.

... But then this happened:

The road to Hell is paved with good intentions– HIV patient gets the one therapy that can cure HIV, dies

An attempt to replicate the results seen in the really functionally cured 'Berlin Patient' did not result in a second person cured of HIV.

It resulted in yet another HIV death.

How? If HIV needs CCR5, and they replaced this patients bone marrow with cells that could not make CCR5, how did he die from AIDS?

Because while HIV likes CCR5 as a co-receptor to infect cells... it doesnt need it. The natural diversity of a patients quasispecies will contain some variants of HIV that can use a different co-receptor, CXCR4.

Viruses that use CXCR4 are assholes.

In this second patient, the radiation/chemo did not kill all of the cells latently infected with CXCR4-tropic viruses. When those viruses 'woke up' in their new environment, and no CCR5-tropic viruses as competition, they went nuts. Oh, and they must have also been resistant to antiretrovirals. For more complications.

So, yeah, the attempt to generate another Berlin Patient, another person 'functionally cured of HIV!'... lead to a mans death.

"Oh my god, what are all those scientists going to do!" I thought. I knew there were a lot of people working on alternative ways of making people delta-CCR5, but if that can kill someone, there was no way they were going to be able to move forward with any clinical trials in people.

Apparently, I was wrong.

:-|

Best of luck to them. But we know what happens with patients treated with maraviroc (a protein that masks CCR5, doesnt delete it)-- The quasispecies figures out a way around it. We know what happens if there is a CXCR4-tropic virus hiding out somewhere when we give someone a delta-CCR5 bone marrow transplant.

Rather than attempting a 'functional cure', I think it would make a lot more sense to use gene-editing technologies as an 'HIV vaccine'-- CCR5 viruses are the ones who 'get through' to establish infection via heterosexual and homosexual contact. CXCR4 viruses dont like doing that. *shrug*

So while an at-risk person might not be born delta-CCR5, does making them kinda-delta-CCR5 (these gene therapy approaches are not perfect) during exposures help them keep from getting infected in the first place? That would be fantastic!

And since you are not fighting with active viral replication and an already-established quasispecies with already established reservoirs, like you would be in an already-infected individual, Id think the risk of ending up with another CXCR4-dead-patient would be virtually non-existant.

But I dont work for this company and no one is asking me. So again, I wish them the best of luck. And I hope no one gets hurt.

sa smith Wed, 04/08/2015 - 13:49

Tags

HIV/AIDS

gene therapy

HIV-1

Very interesting. This is the closest they have got.Although doesn't the HIV mutate its self ? Even if you find a cure for it won't there be another type that will be more resistant to the cure and antiratroviral?14047366

Wow amazing. people that are carriers of HIV have the virus in their body but it does not affect or damage the immune system. when a person have HIV and under go the functional cure of HIV does this make the individual a carrier? this also relate to cancer, are these the only sicknesses that can be maintained by the functional cure?

I agree. To develop a HIV-vaccination and decrease the number of HIV infected persons will have better long term results. Although patient that are already infected will not benefit from this, it will be a better solution for the future.

Nowadays people that suffers from HIV/AIDS lives up to 8 years while being infected with the virus. Antiretroviral strengthens their immune systems enough to fight more common illnesses like Tuberculosis and flu. Thus I think that the focus of scientists must rather be on developing a vaccination than a cure. It makes sense to me to rather decrease the future number of HIV infected patients by vaccination, than to try and develop a cure which only leads to more deaths.
But I think that first the number of HIV infected persons can be drastically reduced if we start to live with precautions. HIV can be prevented by individuals!

15038922

It's great that they are working on finding a cure, but a vaccination makes more sense to me. I understand that there are a lot of humans currently infected with the HIV virus and who has AIDS, and the idea that we can help them in the future pleases me, but wouldn't it be better to spend this time and energy and instead develop a vaccination that can stop the HIV virus altogether? For example, Rabies was stopped by vaccinations, not a cure. If you haven't been properly vaccinated and didn't treat your bite wound by the rabid animal correctly, Rabies will be fatal to you. You cannot cure it if it was in your bloodstream long enough. All of this considered, humans do not fear Rabies like they used to and this is all thanks to vaccinations. Thus wouldn't it just make more sense to stop these experiments that might, or might not kill the patients and just focus on a vaccine? The threat will decrease and then they can work on finding an actual cure to help the people that have been infected.

u15052576

An old saying exists that says, “Prevention is better than cure.” While I believe in finding a cure for HIV, I personally think that scientists’ and researchers’ time would be better spent finding an effective method of prevention that does not deal with education, abstinence and using protection. While I do believe in these methods, I feel that because of how sexually orientated we, as humans, are, sex will always be a popular thing in society. Be it inside or out of wedlock, protected or unprotected, with someone whose sexual history you know or not. This is why I agree with finding a vaccine. A vaccine would be the perfect method of prevention, such that people would not need to change their lifestyle at all. Lifestyle changes are a very tall order, especially for developing countries, as people living in these countries only know their own lifestyle and will not easily change from it. HIV/AIDS is still the most prominent reason for death in Africa and it is not improving. Why not change the way we view solutions? Perhaps this change of thinking will be what saves us eventually. [#15013252]

(See https://cdn1.vox-cdn.com/uploads/chorus_asset/file/2928704/africa_death… and http://www.voxeu.org/article/aids-prevention-abstinence-vs-risk-reducti…)

I do not agree with the idea that scientists should rather be focusing on developing a vaccine than finding a cure because there is such a large population living with the virus. The care of these people should be the priority. Once a cure has been found, we can backtrack and develop a vaccine to prevent further infection. Research into finding a cure and developing a vaccine can take place simultaneously, as long as research into finding a cure is ongoing.

u15014984

Have non of you ever wondered if there weren't already a cure for HIV but it is kept silent, because currently it is almost the only illness that decreases the human population? This may seem silly, but like in TV series there are people manipulating this world. We can cure almost anything except HIV. Its the same with energy sources. There could have been a green way of producing energy for use but maybe the companies who are currently supplying energy bought the "idea" and kept it silent to help themselves survive. Also this may seem negative but there are ways of preventing HIV not even needing to list them. But people still doesn't take it serious for me making it their own problem. If you play with fire you will get burned... Although it will be great if people who were infected due to other causes and those who played with fire and got burned can be helped.

It is better that they find the cure than the vaccination because many people are already infected with the virus. The cure will help people who are already infected and those who will get infected in the future while the vaccination will help people who are not yet infected with the virus.15147208

I am sure the one will lead to the other. It does not have to be either / or. They can research a vaccination as well as a cure. I would like to know how far the research is in finding a vaccination because a lot of material is found on the cure of HIV, but not as much on vaccinations for HIV?

It is so amazing how the Berlin patient was cure do for HIV but very unfortunate how the other patient did not survive the same treatment. I definitely agree that finding a cure is vital and a key tool for eradicating the virus completely in the future. However, prevention is better than cure and the best option currently, until a suitable cure is found. If a discovered vaccine is so effective in preventing HIV, it could give scientists certain clues they might need in developing a cure for the virus and ultimately put less pressure or urgency on them (which may be a reason why finding a cure is so challenging) as they have an effective vaccine to fall back on, which limits the future number of patients that will be infected.

I cant believe that up until today no one has found a cure for HIV. Since I was old enough to make sense of what was going on around me, I was hearing of HIV. I'm so tired, and to think that it is still defeating us! I don't agree with the idea of just finding a vaccine and not going on with the search for a cure, but what about those poor guinea-pigs that are dead? Let's just hope that there will still be people willing to sacrifice themselves to these experiments. But can someone just get it already!

I agree with the idea that "prevention is better than cure" in comment #6 but how are we supposed to rely on preventative methods when it does not seem to be effective currently and also taking into consideration the fact that HIV positive people are not consistent in taking ARV's already?

I do not agree, however, that it may be possible that a cure for HIV may be "kept silent" as mentioned in comment #8 given that HIV is a prominent health concern and considered a epidemic in South Africa. Therefore, with countless deaths already recorded, I doubt that a cure will be "kept silent" at the expense of so many lives.

With regards to the comments made about prevention being better than the cure; I find that to be a bias and unethical view. This is because it suggests that one should save the heathy from getting sick and let the infected die out. Finding a cure is very relevant as this virus can stay in one's body for many years and should be retarded before it can cause further damage in one's body. I find it very exciting that gene therapy is being looked at to put this virus to a halt and that scientists are finally getting closer to creating a 'functional cure'(as the writer would put it).

There is a case I also heard of called "Patent #5676977" which is a so-called cure for AIDS. Many people are unfamiliar with cases such as these and are not familiarized with it. As mentioned in comment #13, possible cures might have been "kept silent" over the past few decades. It is our responsibility to engage in research and "killing the silence" which keeps these cases a secret. And then furthermore, perhaps rather than creating a "vaccine" , they could find a legitimate cure for HIV/AIDS.

I don't necessarily agree that "prevention is better than cure" especially in the context of AIDS today. I do however believe with regards to this article, gene editing technologies would be better used as a "vaccine" as apposed to a cure. If blocking the CCR5 receptor reduces the likeliness of infection then why not?... However the only thing that did come to mind is looking at where HIV takes the biggest toll ...it isn't the areas in which gene therapy and the facilities for it are readily available.. if most of the problem is based in third world countries... i have my doubts as to whether this would be a viable solution

Although the functional cure proved to be fatal for the second patient, it is still an amazing breakthrough in science. if the use of it as a vaccine, rather than a cure, could lead to better results then it should be done. (15038697)

This is very interesting. With regards to comment #8, the thought crossed my mind as well. I then came across the 5676977 Patent, which is a "potential cure". Why has it not been published?

I feel that a vaccine and a cure is needed. A vaccine would only be beneficial to individuals that are HIV negative. But what about the millions of people that are HIV positive? It was a goal in South Africa to produce a HIV-free generation. This could be achieved by scientists working together to developing a cure and a vaccine simultaneously, or making "existing ones" known to the public.

u15092977

I support th view of #6 S Fobian. Research should continue to focus on a vaccination however prevention should be high on priority list. Prevention should not include abstinence and education but a compulsory vaccination from an early age to assist the human body with arming its immune system against HIV AIDS. Furthr to this comment I believe that the government should do more with regards to getting antiretrovirals easily available to the affected people and to have a more controlled approach.

HIV/AIDS is the largest killer in Africa. It is the disease that takes the most lives yearly and weather we develop a cure or a vaccine first does not matter. In both circumstances we are solving the problem.
A vaccine, however, will probably turn out to be the more economic option but a cure will do mounds of good as well. I also feel that HIV/AIDS can be prevented by interventions such as contraception, education and free clinics initiated by governments all around the world.

Considering the comment made by #6 S Fobian, I completely agree. Humans are sexually inclined creatures, the spread of this disease is inevitable without a vaccine.

After reading the blog. I support the view of #6 S Fobian. Research should continue to focus on a vaccination however prevention should be high on priority list. it should be emphasized how important it is. Prevention should not include abstinence and education but a compulsory vaccination from an early age to assist the human body with arming its immune system against HIV AIDS. Further to this comment I believe that the government should do more with regards to getting antivirals easily available to the affected people and to have a more controlled approach.

15003443

Even though I am in favour of research about illnesses, would it really be possible to find a cure for HIV? And is it really worth it to use resources on research for it when it can be used elsewhere where a difference can be made immediately? For instance more than a million people die from malaria a year, where most of the cases are children under the age of 5 years. Would it not be better to try and save their lives, because they can be helped.
Read more about malaria on http://www.unicef.org/health/files/health_africamalaria.pdf
u15006663

I believe that since a cure has not been found for HIV as yet,prevention is the better option for now.Yes people might not always abstain from sexual activity but it is the best option.Vaccination is also a good idea but vaccines are not always the answer.(u15097367)

Referring to comment #8, road injuries and diabetes pretty much kill the same amount of people as HIV, with heart failure and strokes being the most prevalent :
http://www.who.int/mediacentre/factsheets/fs310/en/

In this article what caught my attention the most was that there were some patients that had the CCR5 membrane protein mutation but it had no effect on the functionality of HIV. By developing these treatments are we not increasing the natural selective pressure on HIV? If so, then continued application might only lead to a strain of HIV that is resistant to all treatment types.

I agree. It will be much better for the scientists to invent a vaccine, than to try invent a cure that only kills more people in the process. But I also think that the antiretrovirals have been developed over the years to a treatment that can help patients live much longer with the virus. So I think that if it can be possible to develop a vaccine, it will only be helpful on a long term scale and to eliminate the virus.

As mentioned in a previous comment, Rabies was stopped by vaccinations and not a cure. I feel that with HIV the same can be achieved. Even though there are millions of people suffering with HIV currently, antiretroviral has made the remainder of these peoples lives somewhat manageable. With a vaccination, you ultimately are stopping the HIV in its tracks, unfortunately with human nature comes a lack of responsibility, thus knowing the risk of HIV is real many still do not follow the ABC method and the virus is constantly being spread. With a vaccination this can no longer be possible, and one can only hope that if the vaccination is successful, our great grandchildren will be able to live in a world where HIV isn't a threat.
14392357

Looking at where HIV normally occurs, Africa, It would be more economically sound to produce a vaccine rather than a cure. I have heard so many times that even if a cure was available, only the very affluent would be able to access it and therefore the people who need it the most will still be left in the dark. Therefore i think more focus should be asserted on creating a vaccine rather than a cure.
u15020322

While i agree with most comments on the issue that prevention is better than cure, it is significant to note that there are millions of people currently infected and living with the virus that would disagree with consensus that focus should be on vaccination, the idea of focusing on a vaccine boarders on ethical boundaries while it is logical to “eradicate” the virus for posterity how are their needs more important than the current generation. (#13181620)

Is there any way to find out what co-receptor the HIV uses and then formulate a specific treatment plan according to the result? Or is there a mixture of co-receptors?
[15000614]

Abby, has your blog become some sort of class discussion project for a SA university? You seem to have been flooded by students all debating an issue only tangentially related to the blog post, and appending what seem to be their student IDs to the posts.

On topic: pretty sure this CCR5 gene-editing trials, achieved by a variety of means, are about to go live in the UK. An expensive way to kill your patients if you ask me!

Charl-- Yup! Its happened before, and I asked them to tell me about the class/project, and nobody responded. LOL! But some kids are learning something, maybe, so Ill take it.

I dont have a good feeling about these trials, and I wouldnt personally be involved in one post-infection. Gene therapy that has worked 'works' best when you dont need very good efficiency. The treatment for Hemophilia B, for example. But 'inefficiency' translates into 'minor inconvenience' for HIV. :-/

I don’t agree with the statement that medical scientists should rather put all their time into developing a vaccine than to find a cure for HIV and AIDS. The disease is spread by the people who are infected by the virus (There is a huge percentage of people who are infected by it). Therefore the people must be their main focus and not the vaccine. Because when they are cured the virus will not be able to spread. Vaccine as we all know is not 100% guaranteed the prevent us from been infected. And that’s why they should find a cure.
15021212

*pointsup*

See? Not gonna clue us in. Leave their required comment and movin on, LOL!!!

It shouldnt be about which aspect should require more time, money or research. The positive results that have been seen in vaccination research have been in my opinion of more ‘scientifc weight’ such as these naturally produced neutralizing antibodies. Creating antibodies and using simple biochemical mechanisms like this gives us an advantage with speed and amount of experimentation that can take place which will then only increase reliability of any results. This should and probably will receive alot more research, more or less, than a cure currently suffering people ? thats for the people with the money to decide…
u11071142

If finding a cure 5 years from now meant having to proceed with the current methods of treatments then I would be for it. Unfortunately, there is no way to guarantee when a reliable, easily-accessible cure will be found and therefore diverting all efforts strictly to research in that direction (looking for a cure) would be a gamble that could go either way.
Changes need to made on an evolutionary basis.

u12001113

Seeing as though the AIDS virus thrives in the human body and does not do to well in alternate conditions would it be possible for the inner conditions of humans to be altered for a short period of time in order to kill off the virus ad thereafter return the body back to its original conditions ? For example the virus likes pH conditions between 7 and 8 so altering this may kill it off.

Doesn't the HIV virus replicate itself every time? Its one of the viruses that show that evolution is still happening.

Re #8 and 15:
The only way to "keep silent" an actual vaccine or cure for AIDS would be for everyone involved to be an evil, sociopathic monster. People go into HIV/AIDS research because they care, deeply, about all the people affected by this disease. To imply that they would then 'hide' a cure from the world is whole improbable. Why would anyone do that? A cure for AIDS, a working vaccine for HIV, that's an instant Nobel prize right there.

As someone who spent years working on an HIV vaccine (that didn't work), it makes me really really angry when people imply 1) that it should be easy, and if we haven't found a vaccine by now it's because we aren't working hard enough (#12) 2) that every researcher is some kind of monster, hiding cures from the world.

Wow! This is the closest that they have ever gotten, its unbelievable how no one has found a cure for the disease with the amount of research projects around the world and with most of the top scientists working on the cure, but this just shows how much science has improved over the last few years.
15137717

It seem is new knowledge that trials were performed on human beings that were actually infected but was not aware that the experiment resulted in death indicating that this is not a discovery of a possible cure. However this is exciting as science has revealed certain key components such as ccr5 that will draw us not only to a possible HIV vaccine but a way of eradicating HIV completely
(u14018676).

How to deal with the SA comments next time they pop up: announce in the comment thread that you have picked 5 people at random (identified by the student numbers they leave), and deleted/withheld their comments (and will do the same to their future comments). Hold these ransom until someone (preferably the course coordinator) explains why they're turning your blog into an HIV101DERP assignment.

On topic: if you're going to do some gene editing for vaccination, surely something like the Farzan work (http://www.nature.com/nature/journal/v519/n7541/abs/nature14264.html) is more sensible?

Against all odds I believe that the invention of a vaccine to this virus would be the best option. I think no one would want to risk the chance of being infected by this virus. Rather prevent it before hand. It is always better to be a step ahead of the disease[15092314]

I believe that the invention of the vaccination will definitely decrease the number of HIV cases in the world, however, having said that, the vaccination will not be able to cure people who already have the virus.

A new, out-of-left-field way to fight HIV. Maybe?

sa smith — Wed, 10 Dec 2014 12:00:58 +0000

A new, out-of-left-field way to fight HIV. Maybe?

New, weird, out-of-left-field, ideas-- we need them to stop HIV.

This one makes sense, in retrospect, but I wouldnt have thought to try what these folks did:

Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection

Background info: HIV loves to rip through CD4+ T-cells in gut-associated lymphoid tissue. Early in infection, HIV tears those cells up, and anything HIV doesnt kill, it digs in as a latent reservoir to pop out more babby viruses later. Doesnt matter if you ultimately take anti-retrovirals, the damage is done early in infection, and things never go back to 'normal'. (more info).

Maybe you can stop/limit HIV infection by keeping GALT CD4+ T-cells from running around like chickens with their heads cut off?

Maybe?

But how would you even go about doing that?

Some immune cells, like CD4+ T-cells, roll round your body. Where they are needed, cells will express integrins to slow down their rolling. The immune cell then smooshes itself through the cell barrier to get where it needs to go. Remember that animation from XVIVO a while back?

So, maybe stop CD4+ T-cells from moving around by blocking the interactions between the cell and the integrins.

It turns out there is already a drug in clinical trails that can do that: An anti-alpha4beta7 antibody, AMG 181/MEDI-7183, made by Astrazeneca (more info about these drugs here-- I think this is OA).

Astrazeneca is using it for Crohns disease and ulcerative colitis, but no reason it cant be tried with HIV, right?

Well, apparently, this idea kinda works.

When monkeys were given monkey-version of the anti-a4b7 antibody, then vaginally challenged with SIV, 10 of 12 control monkeys got infected, whereas 6 of 12 treated animals got infected. And the treated animals only got infected after repeated challenges-- early in the experiment (weak 5), only 1 of 12 got infected, whereas the 10 infected control animals were all infected by then. They had to keep exposing the animals to virus over and over to get the number up to 6 in the treated animals.

Furthermore, the treated infected animals were able to keep their CD4+ T-cell levels up, while the untreated animals had their numbers tank. As to what this could mean for disease prognosis if someone takes this treatment, but still becomes infected, they noted that in their previous work with this antibody for 'treating' SIV in monkeys:

Notably, whereas 10 of 12 controls died of AIDS within 2 years, all ten treated animals remained
healthy with CD4+ T cell counts >500/µl 5 years after infection.

So, maybe, if you take this treatment, but you still get infected, you might progress from HIV-->AIDS very slowly, if at all.

Maybe.

Remember, folks, these are studies in a few dozen monkeys!

We are a loooong way from this being in people, even with Phase 1 clinical trials already completed.

We have no clue *HOW* this therapy works. They have great ideas-- In the treated but infected animals, HIV was hanging out at the site of infection, and was found less frequently in the GALT. Maybe the treatment kept new targets from the site of infection? Maybe it kept infected CD4+ cells from creeping around and infecting other CD4+ T-cell hot-spots? Maybe the antibody straight-up interferes with SIV binding to target cells?

We dont know what dose to give people. We dont know whether it HAS to be injected, or whether it could work as a local gel. We dont know what potential side-effects there are (what if you are on this treatment, and get the flu?). We dont know whats up with the viruses that could overcome the treatment. We dont know how to give this treatment to people who are already infected (how do anti-retrovirals play into this? would PREP compliment this, or not?).

We dont know a lot.

But its something that seems to kinda work, it doesnt target the virus (a ticking time-bomb with HIV-- works for a while, then HIV figures out a way around it), and its passed Phase I clinical trials already.

We always need new weapons against HIV-- I hope this one pans out.

sa smith Wed, 12/10/2014 - 07:00

Tags

HIV/AIDS

HIV-1

I think this is OA

Nope. There are some decent-looking choices in the "related papers" category, though.

Well, you can't treat HIV patients with natalizumab.

Because of the risk of PML (as it originally found in AIDS patients, but is commonly associated with natalizumab as it suppresses immunosurvellience of the brain), but vedolizumab doesn't cause it in more than 3000 patients in clinical trials for 6 years.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038524/ (safety and tolerability of vedolizumab)

GMO HIV-- Still helping kids with relapsed acute lymphoblastic leukemia

sa smith — Tue, 09 Dec 2014 11:00:27 +0000

GMO HIV-- Still helping kids with relapsed acute lymphoblastic leukemia

Five kids in the first trial.

Then eleven.

Now thirty (ultimately 39):

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia

Slowly but surely, HIV genetically modified to genetically modify relapsed acute lymphoblastic leukemia (ALL) patients T-cells are prolonging (saving?) kids lives.

Ive written about this treatment a couple times before:

‘Dismal prognosis’ with leukemia? Nothing a GMO virus cant fix.

GMO virus vs B-Cell Acute Lymphoblastic Leukemia: Why is this not a standard therapy yet??

Basically, scientists get HIV to teach cancer patients Cytotoxic T-cells how to kill the cancer that is killing them. Normally T-cells bumble around, using random mutation and natural selection to 'figure out' how to kill cells infected with a pathogen. But due to the nature of our immune system, they dont like/cant 'figure out' how to kill some cancer cells. Why? Because cancer is us gone wrong, and CTLs are trained not to kill *us*.

CTLs would never figure out how to target the protein these GMO T-cells see: CD19.

CD19 is a totally normal protein on the surface of B-cells. There is no *way* T-cells would start recognizing CD19-->killing CD19+ cells... even if those CD19+ cells were a cancer killing us. CD19 is *normal*.

Here is where HIV comes in handy!

Get HIV to deliver the gene coding for a protein that recognizes CD19, and has the signaling capabilities of a T-cell receptor! Its a cheat-sheet. "Here, CTL. You will never figure out how to do this on your own. Here is the answer."

In this trial, they treated 30 kids/adults with relapsed acute lymphoblastic leukemia (they had ALL, got various treatments, nothing was working at keeping the ALL at bay).

27 of 30 responded to the initial therapy to achieve remission. These patients entered this trial out of options, and in all doubt, this therapy bought them some time. And this time was bought with not-too-bad side-effects-- cytokine-release syndrome. You feel like crap for a bit while your GMO T-cells are killing the cancer. But that resolves, and even severe cytokine-release syndrome is manageable.

This group just presented new results, saying that 10 of their (ultimately) 39 patients relapsed. This therapy did not 'cure' everyone. But like I said, it bought time... for some (five of those ten relapsed patients died).

However, 69% of the patients were relapse-free at 6 months. This allowed the researchers to do some statistics-- They estimate a ~70% chance of survival at 2 years post-treatment. Basically, with this treatment, if you make it 6-months, they think youre going to do okay, at least for a while. This treatment is mainly for kids, and who knows what is going to happen in 20, 40, 80 years.

But for all the time HIV has stolen from people, from families, its nice to see it giving some time back.

sa smith Tue, 12/09/2014 - 06:00

Tags

"We are the Borg. Your biological and technological distinctiveness will be added to our own. Resistance is futile."

Interesting work. In the trial was there not a danger that the CTL could start killing normal cells since it initially perceived the cancer cells as "normal" ? Do you perhaps know what could have caused the ten patients to relapse? In those ten patients what further went wrong in the five that died?

It's about time HIV is used for good after all the hurt it caused the world. Good work , good work indeed.

'HIV infection en route to endogenization: two cases' facepalm

sa smith — Fri, 05 Dec 2014 12:26:08 +0000

'HIV infection en route to endogenization: two cases' *facepalm*

For some reason, pop news became enamored with this paper last month (unfortunately while I was away at a conference):

HIV infection en route to endogenization: two cases

Inexplicable media frenzy--

Scientists find mechanism for spontaneous HIV cure

French scientists find genetic mechanism by which two men were spontaneously cured of HIV.

HIV discovery offers new lead in finding cure

I have a lot of problems with this paper. Starting with the first sentence.

The long-term spontaneous evolution between humans and the human immunodeficiency virus (HIV) is not well characterized.

"Spontaneous evolution"? Wat? Do they mean basic co-evolution of HIV and humans? While the field hasnt 'done everything', co-evolution has been explored, to the point where I have written about it on my blog (which covers only the smallest percentage of HIV papers).

And this paper doesnt improve at all from there. I mean basic stuff like descriptions of reagents used (peptide library. neat. WHICH ONE?) This paper is functionally useless to me.

But because they issued some press release, every pop news outlet from MSN to Al Jazeera was talking about their paper, and now I have to to dispel some flat-out bad science.

1-- Are these two people 'cured' of HIV/AIDS?

No. Nothing in this paper suggests they are. The two patients are long-term non-progressors.

2-- Is HIV becoming an endogenous retrovirus?

No.

Firstly, there are very, very, very few endogenous lentiviruses. There is something about them that is not conducive to endogenization. There are no endogenous SIVs in primate populations that have been co-evolving with their SIVs for much longer than humans ~100 years with HIV (the 'best' we have in that lemur ERV, linked above). In fact pin-pointing exactly how old HIV/SIV viruses are has been extremely difficult because of this, so scientists have had to study the evolution of SIV in geographically/temporally isolated colonies of animals, and study the evolution of primate genomes to extrapolate the age of SIV-like retroviruses:

Paleovirology– HIV-1s ancestors just got older

HIV-1s ancestors just got older-er

Indeed the 'example' they gave in this paper is the retrovirus in the process of endogenization in Koalas, is a gammaretrovirus. Another common example-- MMTV in mice-- is a betatretrovirus. Gammas and betas are the retroviruses that tolerate being endogenized 'the best', and even *then* it is an accident. To people not familiar with retroviurses, theyre all just 'retroviruses', when in reality, they are two entirely different creatures.

There is also nothing, nothing, in this paper that suggests HIV is becoming an ERV. Nothing. Step 1 would be sequencing the genomes of sperm. Is HIV getting into sperm genomes, thus potentially creating an ERV? No idea. They didnt look.

Is there a child born to an HIV+ mother who is 'HIV+', and has 'HIV+' skin cells, liver cells, smooth muscle cells, etc and no immune response to HIV? Cause that would be evidence for endogenization!

But they dont have anything like that.

However, because I want you readers to learn SOMETHING for clicking on this post, Im going to thought-experiment-answer a third question:

3-- Is an HIV ERV a cure for HIV?

Again, this is thought-experiment country, here.

With MMTV, having endogenous MMTVs can protect against infection from exogenous MMTVs. The key here is how. Well, your immune system automatically kills developing immune cells that recognize 'self'. If you have an ERV active at the right place/right time, your immune system will kill any immune cell that recognize the retroviral proteins.

With MMTV, the protein of interest is 'SAg'. Exogenous MMTV needs the immune system to react to SAg to establish infection. But if there is an endogenous MMTV, any immune cell that sees MMTV SAg will be killed. No immune reaction=Protection from exogenous infection.

Maybe.

Because sometimes an endogenous MMTV leaves a mouse *more* susceptible to infection.

Getting back to HIV-- HIV does not have a protein homologous to MMTV SAg, because HIV and MMTV are not the same creature.

I think a likely outcome from an endogenous HIV would be... nothing.

The world-wide HIV quasispecies is so diverse, its likely that one would be exposed to an exogenous HIV that looked nothing like the endogenous HIV (ie, the reason why we have a hard time making an HIV vaccine). An endogenous HIV would look so different from the HIV a person was actually exposed to, that any negative selection of B- and T-cells would likely be pointless.

IF the exogenous and endogenous were similar enough, you would still be infected with HIV, but have fewer CD4+ and CD8+ and B-cells that could be activated to fight that infection. Now, a lot of the 'problems' with HIV/AIDS come from an over-activated immune system, so maybe no reaction would be a good thing? But you are not going to clear an infection by not fighting it, either.

None of this equals endogenous HIV as a cure for HIV.

Even for fun, I cannot think of a pathway from endogenous HIV-->CURE, and there is nothing in this paper to help us make that connection.

sa smith Fri, 12/05/2014 - 07:26

Tags

HIV-1 evolution: ‘Badder’ still isnt ‘Better’

sa smith — Thu, 04 Dec 2014 17:39:57 +0000

HIV-1 evolution: ‘Badder’ still isnt ‘Better’

I write about lots of things on ERV, but I didnt anticipate ever getting to the point where I can write new blog posts on new publications by cutting and pasting from old blog posts on old papers...

Lots of news outlets have been talking about this new paper:

Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence

Ive covered the themes of this paper several times in the past.

1-- Some people progress to AIDS after HIV infection, some dont, or do so slowly. One of the reasons why one person might not progress to AIDS would be their particular MHC Class I allele (what 'flavor' of MHC Class I you inherited from your parents).

2-- HIV-1 is adapting to this MHC Class I selective pressure. We would LOVE to have an HIV vaccine that protected people by training their immune systems to see bits and pieces of HIV in MHC Class I, but that window is closing.

3-- HIV-1 adapting to humans does not mean it is becoming more pathogenic. In fact, we would not expect HIV to follow that particular trajectory. That has happened in no other SIV-primate. In every other primate, co-evolution with SIV has led to a sort of mutual 'Meh.' And, studies specifically addressing the evolution of HIV fitness in humans have found that HIV is doing the same in humans.

This paper is more data to support some older ideas in HIV. While I dont quite understand the media frenzy, with HIV, you cant ever assume things or take old ideas for granted, so I am quite happy they performed this work.

sa smith Thu, 12/04/2014 - 12:39

Tags

evolution

HIV/AIDS

HIV-1

I've been kind of surprised that antivaccine crank Cynthia "CIA" Parker hasn't stapled this to her freak flag yet. I wish I had noticed Fig. S3D earlier.

I read somewhere( Peter Cresswell,December 23, 2014, The first step of peptide selection in antigen presentation by MHC classI molecules) that the MHC class I molecules select and present a limited set of antigen peptides from a vast that are provided. So MHC class I molecules technically go through rounds of considering and rejecting peptides until peptides with high affinity are acquired for presentation. This explains the effect on the progression of HIV.
15073883

How do you get tested for which MHC molecule you have?

Why do scientists always forget about luck?

sa smith — Mon, 29 Sep 2014 14:41:59 +0000

Why do scientists always forget about luck?

You get the data when you get the data, but the information we get from this study would have been useful several years ago:

Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant

The Berlin Patient-- Guy gets HIV, develops a blood cancer, gets radiation and chemo for the cancer, a bone marrow transplant from someone who lacks the CCR5 receptor-- one of the co-receptors HIV prefers to use to infect our cells. Years later, he is still HIV free.

How did this procedure work?

The factors thought to be involved in the favorable outcome of the Berlin patient following HSCT include (i) the myeloablative conditioning regimen; (ii) the donor's homozygosity for Δ32ccr5; and (iii) the graft versus host effect.

Did the radiation/chemo kill all the HIV+ cells?

Was having a CCR5-free donor key?

Did the donor cells kill all the residual patient immune cells (and any that were infected with HIV)?

This paper made things as simple as possible to see what happened--

1-- Took 'donor' bone marrow from monkeys.

2-- Infected the monkeys with HIV/SIV (SHIV).

3-- Gave the monkeys 'cancer treatment' (radiation).

4-- Gave them their own bone marrow back.

After the monkeys were taken off of antiretrovirals........ the virus came back.

So, we know 'cancer treatment' alone is not enough to kill 100% of the reservoir HIV infected cells.

Like I said, you get the data when you get the data, but this is information that would have been useful several years ago.

This paper very directly tests an idea we have only inferred from patients before-- radiation isnt enough. They eliminated the other variables. This is essential information. Good on these folks for systematically testing these questions on primates instead of their patients, but dammit, do it faster.

We have been answering these questions by testing alternative therapies on humans. We know that HIV patients who get radiation/chemo still have the virus bounce back, even with graft-vs-host responses. We know CCR5-negative donors are necessary-- thats why they kept those two guys on antiviral therapy via their cancer treatment with a CCR5-positive donor. That would have worked extremely well, if their physicians had not, bafflingly, suggested they go off the antiviral therapy. If someone had performed this papers experiments earlier, these men might not have ever gone off of treatment.

We also know CCR5-negative donors arent enough, and could, in fact, allow CXCR4 viruses thrive and kill the patient, shockingly quickly. With this outcome, Im not sure it is even ethical to try another CCR5-negative transplant, and Im not sure where it puts the scientists who have developed ways of using gene therapy to 'make' people CCR5 negative. People studying the fundamental concepts behind how, potentially, the Berlin Patient was cured, might have revealed problems like this in animal trials, and prevented this mans death.

More labs focusing on the fundamentals of how this virus works can only decrease the 'set-backs' we have seen seemingly with increasing frequency recently, in humans.

But I think studying how the virus works under these circumstances, and what contributed to curing *The Berlin Patient* are different questions.

What specifically happened in The Berlin Patient was almost certainly a combination of the radiation/chemo, graft-host responses, having a CCR5-negative donor...

And dumb luck.

The Berlin patient could, and frankly, should have, statistically, have ended up like the patient who died a year after the 'miracle' transplant... but he didnt. Which means either 1) he was lucky enough to be treated before his quasispecies expanded to include CXCR4 variants, or 2) his radiation/chemo/graft-vs-host luckily killed any CXCR4 infected cells by chance, or 3) there are CXCR4 infected cells sitting quietly somewhere in his body, and the only reason they havent reactivated, releasing CXCR4 viruses out to kill him, is luck.

We can test all of those hypotheses, but the Berlin Patient lasting this long wasnt due to thoughtful consideration of these possibilities and treatment designed to maximize his chances.

It was dumb luck.

sa smith Mon, 09/29/2014 - 10:41

Tags

HIV/AIDS

HIV-1

That is, unfortunately, a perfectly good explanation. But - wouldn't it be cool if it was not "just" dumb luck?

CRISPR CAS has begun to revolutionize scientific research and there are exciting possibilities of using it therapeutically. Some groups have made AAV that are used to infect mice in order to delete a host gene. Do you think that genome editing might be a better way to delete CCR5 (or a piece of it) rather than through bone marrow transplant? Do you think this would solve the problem of having to deplete existing cellular subsets?

Hi Brandt!

I think the folks trying to delete CCR5 are dead in the water for HIV+ people, after the guy who got a delta32 bone marrow transplant died. They have no way of knowing whether they will do the same thing to their patients (get rid of CCR5-tropic viruses, CXCR4 thrive without the competition, kill the patient).

They might still have a viable therapy pre-exposure (CCR5-tropic viruses get through, CXCR4 dont... usually...), but then you have to get trials to approve a therapy that has no proven immediate benefit to the patient.

I feel really bad for those researchers, right now. They had a real cool idea going.

It sounds like research may eventually lead to a greater ability to handle HIV, but probably with great difficulty.

Dunno anything about virology myself, but it seems that this and other African forest sources virii (Marburg etc) are best left there, and should have been quarantined by whatever mild or wild means needed until they drop below 1:1 -- carriers each transmit to less than one other person.

Allowing this stuff to travel through the population is like picking a fight with a bear while thinking "I have a plasma gun kit in my backpack".
In the foreseeable future we can lessen the impact of HIV but it will neither be eradicated nor controlled.

ERVs vs HIV-- Maybe a bad idea

sa smith — Wed, 24 Sep 2014 11:45:53 +0000

ERVs vs HIV-- Maybe a bad idea

For quite a while, now, there has been a connection between Endogenous Retroviruses and HIV. For some unknown reason, some of the young ERVs in humans, the ones that can still code for a protein here and there, are reactivated in HIV+ patients. Scientists have found ERV RNA in HIV+ patient plasma, and they have even found cytotoxic T-cells that target ERV proteins.

HIVs controlled by HERVs

This lead some scientists to believe that maybe, maybe, ERVs could be a good target for an anti-HIV therapy.

HIV changes a lot. It is really hard to train your immune system to fight it.

ERVs are 'human', now. Which means they are 'self', and attacking them could be bad (it would be a kind of purposeful autoimmunity), but because the ERVs are 'human', they wont mutate much. HIV is a moving target. Targeting the ERV activated by HIV infection could be a non-moving alternative anti-HIV target.

HERVs and HIV-1

Bad news. Targeting ERVs as a 'sneak attack' on HIV is probably a bad idea.

HIV-1 Infection Leads to Increased Transcription of Human Endogenous Retrovirus HERV-K (HML-2) Proviruses In Vivo but Not to Increased Virion Production

The problem is, we dont know exactly how or why ERV RNA/DNA/proteins are being expressed in HIV+ individuals.

If it is something very very specific, something that only happens in a CD4+ T-cell in direct response to that being infected by HIV, that would mean targeting the ERV is a great idea. You could train the HIV+ individuals immune system to 'see' the ERV components in an HIV infected CD4+ T-cell, and BAM! Kill the HIV infected cell!

BUT, if it is something very very broad-- like, over activation of the immune system leads to wide-spread disregulation and expression of ERV RNA/DNA/proteins, that would be targeting ERVs is a terrible idea. If you trained the HIV+ individuals immune system to 'see' ERV components... the immune system could not only target the HIV infected cells, but also other immune cells-- The B-cells the patient needs to fight HIV, the CTL cells the patient needs to fight HIV, the CD4+ T-cells the patient is trying to preserve... and who knows what else.

In this paper, they still havent nailed down *WHY* ERV components are expressed in HIV+ individuals, but they did determine that ERV activation is broad.

... total PBMCs from HIV-infected and uninfected patients were sorted into CD4+ and CD8+ T cell subsets, in addition to B cells and monocytes. These cell types represent the major constituents of PBMCs, although smaller populations, including dendritic cells and NK cells, could potentially represent sources of HML-2 expression. When HML-2 RNA upregulation was assessed in sorted cells, we saw no significant difference in expression in any subset from HIV patients compared to controls, although each subset individually showed a small increase in patients compared to controls, with the greatest difference in monocytes, a cell type that is not a target for HIV infection in vivo (59). The lack of enrichment in the CD4+ T cell population is consistent with HML-2 RNA expression having no clear relationship to HIV replication (Fig. 4), while the lack of enrichment in other cell populations could exemplify the indirect mechanism regulating HML-2 expression in HIV-1-infected patients. The differences in the magnitude of HML-2 transcription in cell subsets could be due to cell-specific transcription factors, methylation patterns, or other epigenetic changes, which are believed to control endogenous retrovirus expression in differentiated tissues (60, 61). Based on these results, it appears that differential expression from multiple cell sources may lead to the 2-fold difference in HML-2 expression in HIV-infected versus control individuals.

There was a slight increase in ERV RNA in each cell type in HIV+ vs controls. The difference between HIV+ and control is all of these little differences adding together, NOT because ERV RNA is expressed in HIV infected CD4+ T-cells.

Based on these observations, it appears that the use of HML-2 expression as a way to target HIV infection carries a significant risk of off-target effects. Our data suggest that HML-2 protein may be expressed in CD8+ T cells and B cells. Thus, targeting HML-2 epitopes may affect these cells and weaken the cytotoxic and humoral arms of an individual's immune response to HIV-1 infection (69).

Damn.

sa smith Wed, 09/24/2014 - 07:45

Tags

How very interesting

awesome blog. i believe it's only when HIV decides to take the plunge and become an ERV, i.e., integrate into our germline, that HIV will spell the beginning of it's end, as we currently know it. i once heard Will Taylor refer to HIV as a "fallen angel". that comment fits well with your blog tagline. i wonder what HIV will create in us if and when it does become an ERV????????