viruses

Just how long does the Ebola virus linger in semen?

tsmith — Tue, 27 Sep 2016 12:26:19 +0000

Just how long does the Ebola virus linger in semen?

The 2013-2016 West African Ebola virus outbreak altered our perception of just what an Ebola outbreak could look like.

While none of the three primary affected countries--Liberia, Sierra Leone, and Guinea-have had a case since April 2016, the outbreak resulted in a total of over 28,000 cases of Ebola virus disease (EVD)--65 times higher than the previous largest EVD outbreak, and more than 15 times the total number of cases of all prior EVD outbreaks combined, from the virus's discovery in 1976 to a concurrent (but unrelated) outbreak in the Democratic Republic of Congo in 2014.

In March 2016, cases were identified once again in both Liberia and Guinea, just after the outbreak had been declared over. Both countries were declared Ebola-free in June 2016; Guinea for the second time and Liberia for the fourth time. The last series of cases in these countries demonstrated just how different this epidemic was from prior ones, changing what we thought we knew about the virus:

Previous research suggested Ebola could persist in the semen for 40 to 90 days. But that window has been eclipsed in this epidemic by a considerable amount. A probable case of sexual transmission occurred approximately six months after the patient’s initial infection last year in Liberia. Another study found evidence of Ebola in the semen of 25% of surviving men tested seven to nine months after infection. And it takes only a single transmission to kick off a fresh recurrence of the disease.

A recent paper extended this window of virus persistence in the semen even longer--over 500 days. It also explains how the outbreaks began in both countries after being declared Ebola-free--so where did the virus come from?

In a convergence of old-fashioned, "shoe leather" epidemiology/tracing of cases and viral genomics, two converging lines of evidence led to the identification of the same individual: a man who had been confirmed as an EVD case in 2014, and had sexual contact with one of the new cases. Author Nick Loman discussed via email:

The epidemiologists told us independently that they had identified a survivor and we were amazed when we decoded the metadata to find that case was indeed the same person. The sequencing and epidemiology is tightly coordinated via Guinea's Ministry of Health who ran National Coordination for the Ebola outbreak and the World Health Organisation.

It shows that the genomics and epidemiology works best when working hand-in-hand. If we’d just had the genomics or the epidemiology we’d still have an element of doubt.

The sequencing results also suggested that it was likely that the new viral outbreak was caused by this survivor, and unlikely that the outbreak was due to another "spillover" of the virus from the local animal population, according to author Andrew Rambaut:

If the virus was present in bats and jumped to humans again in 2016, it might be genetically similar to the viruses in the human outbreak but not have any of the mutations that uniquely arose in the human outbreak (it would have its own unique mutations that had arisen in the bat population since the virus that caused human epidemic).

It might be possible that the virus jumped from humans to some animal reservoir in the region and then back to humans in 2016 but because we have the virus sequence from the patients acute disease 15 months earlier we can see that it essentially exactly the same virus. So this makes it certain the virus was persisting in this individual for the period.

So the virus--persisting in the survivor's semen for at least 531 days--sparked a new wave of cases. Ebola researcher Daniel Bausch noted elsewhere that “The virus does seem to persist longer than we’ve ever recognized before. Sexual transmission still seems to be rare, but the sample size of survivors now is so much larger than we’ve ever had before (maybe 3,000-5,000 sexually active males versus 50-100 for the largest previous outbreak) that we’re picking up rare events.”

And we're now actively looking for those rare events, too. The Liberia Men's Health Screening Program already reports detection of Ebola virus in the semen at 565 days following symptoms, suggesting we will need to remain vigilant about survivors in both this and any future EVD epidemics. The challenges are clear--we need to investigate EVD survivors as patients, research participants, and possible viral reservoirs--each of which comes with unique difficulties. By continuing to learn as much as we can from this outbreak, perhaps we can contain future outbreaks more quickly--and prevent others from igniting.

tsmith Tue, 09/27/2016 - 08:26

Tags

ebola

General Epidemiology

infectious disease

outbreak

Oh wow. That transmission method is going to make this disease even harder to stay on top of. I can't imagine getting compliance from every man who survived Ebola to not have sex for 2 years (or more!).

The only thing I can hope is that this increases the acceptability of condom use (male and female) in the area.

It probably won't help the stigmatization and isolation of survivors.

Yes, stigma remains a big issue that wasn't really addressed. Condom use is definitely being recommended but I don't know how well that message has been received. And even then, recommendations previously were for "a few months" then "6 months" and now...a year? 2 years? forever? There's going to be a lot of confusion.

Very interesting article!! I had actually no idea about the severity of the Ebola virus until the 2014 outbreak!! It seems unreal that the virus can be carried that long in the semen and is kind of scary that it is possible in case of another outbreak that seems like it would be very hard to control the sexual activity of every man with the virus!!

Zika virus, drug discovery, and student projects

sporte — Tue, 08 Mar 2016 23:10:56 +0000

Zika virus, drug discovery, and student projects

It's well understood in science education that students are more engaged when they work on problems that matter. Right now, Zika virus matters. Zika is a very scary problem that matters a great deal to anyone who might want to start a family and greatly concerns my students.

I teach a bioinformatics course where students use computational tools to research biology. Since my students are learning how to use tools that can be applied to this problem, I decided to have them apply their new bioinformatics skills to identify drugs that work against Zika virus.

We don't have the lab facilities to test drug candidates, but it's nice for students to realize they're learning skills that could be put to use.

Here's what we're doing:

Looking at background information about Zika virus.
Using blastp to identify related proteins that are also bound to drugs.
Using molecular modeling to see if those drugs might also bind to Zika virus proteins.

Getting up-to-speed on Zika virus

We found a great compilation of Zika resources at the NCBI. CIDRAP has a great set of Zika resources as well.

My students go to the NCBI Zika resource, select the link to publications, and scan the titles to see what's new. This list is a bit overwhelming, so I ask them to focus on the first and last sentences in the abstract from P. Brasil et. al., Zika Virus Infection in Pregnant Women in Rio de Janeiro, and on this publication from Tang, et. al. They need to identify birth defects associated with Zika virus infection and summarize two kinds of data that support the association between infection and birth defects.

Next, they use the Health Map link to see where infections are occurring. It gets more personal when you see cases happening in your state.

Health Map shows Zika virus cases in real time.

We also look at the ViralZone page from Expasy to learn about the Zika life cycle and see how the Zika polyprotein gets chopped into smaller parts. This has a link to an interesting Wikipedia page for a Zika virus receptor (DC-SIGN or CD209) that appears to be expressed in the uterus and on brain cells–at least that's my interpretation of the RNA expression data.

But, it's easy to get lost clicking too many links, so we go on to protein blast.

Identifying potential drug targets with BLAST

I think the easiest way to find a drug against a virus is to start by looking at compounds we already know about. We know that many successful antiviral drugs target viral proteases and polymerases, so my students go to the Zika virus reference genome (thanks NCBI!) and get the protein sequences for the Zika virus protease NS3 and the Zika virus RNA dependent RNA polymerase.

Then they use protein blast to search the NCBI structure database and see if there are 3D structures from related viruses that are bound to drugs.

Once they've found a structure to work with, they reverse the search and use blastp to compare their new sequence to the sequence of the Zika protein.

Using molecular models to see if drugs might bind to Zika virus

Once our students have found structures that contain a drug, they look at amino acids that are near the drug to see if those residues are similar to those in Zika virus.

Would Sovaldi® (Sofosbuvir) work against Zika virus?

Whenever possible, I like to give examples to show an investigation might work. When I noticed that some of my blast results included proteins from Hepatitis C virus, I decided to use this as an example. There's a drug that works by inhibiting the RNA polymerase in Hepatitis C (Sovaldi® from Gilead), so I decided to find out if it might work against Zika as well.

Hepatitis C virus RNA polymerase bound to Sovadi® (Sofosbuvir) from 4WTG colored by charge.

First, I did a blastp search and compared the protein sequence from the structure 4WTG against Zika virus RNA polymerase.

blastp results from comparing Zika virus RNA polymerase to the Hepatitis C virus polymerase in 4WTG.

Only 25% of the amino acids are identical, but the E value is 0.007, so that's encouraging. I decided to take a closer look.

I used 4WTG as a query sequence in blastp to align it to the Zika virus polymerase sequence. Then, I downloaded the 4WTG structure and opened it in Molecule World. I selected the drug and used the Select Nearby feature to identify amino acids that might be bound to the drug. Returning to the aligned sequences, I highlighted those amino acids in the alignment.

Interestingly, the drug binds to amino acids that are present in the same positions in both Zika virus RNA polymerase and in the Hepatitis C virus RNA polymerase. Cool!

I took a closer look. In the top image, two manganese atoms bound to the drug are also bound to aspartic acid residues. These are present in both proteins.

Amino acids that interact with Sovaldi® are colored by residue in Molecule World and drawn as tubes.

In the bottom image, I can see an arginine that's present in both proteins. Here, it appears to participate in an ionic interaction with the drug.

Amino acids that interact with Sovaldi® are drawn with in a space filling mode and colored by element in Molecule World.

Now, these models don't prove that Sovaldi would inhibit Zika virus replication. But it might be worth taking a look. If I were culturing brain stem cells like Tang, et. al (3), I might take out a loan to buy some Sovaldi® and add it to the growth medium. Just to see what happens.

For now, I'm looking forward to seeing what my students find.

Note: All the molecular modeling work described here was carried out with the Molecule World iPad app from Digital World Biology.

References:

The Zika Virus Resource at the National Center for Biotechnology Information
Brasil P, et.al. Zika Virus Infection in Pregnant Women in Rio de Janeiro N Engl J Med. 2016 Mar 4. [Epub ahead of print]
Tang et al., Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth, Cell Stem Cell (2016), http://dx.doi.org/10.1016/j.stem.2016.02.016
Stephen F. Altschul, Thomas L. Madden, Alejandro A. Schäffer, Jinghui Zhang, Zheng Zhang, Webb Miller, and David J. Lipman (1997), "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs", Nucleic Acids Res. 25:3389-3402.
Appleby TC, Perry JK, Murakami E, Barauskas O, Feng J, Cho A, Fox D 3rd,
Wetmore DR, McGrath ME, Ray AS, Sofia MJ, Swaminathan S, Edwards TE. Viral
replication. Structural basis for RNA replication by the hepatitis C virus
polymerase. Science. 2015 Feb 13;347(6223):771-5. doi: 10.1126/science.1259210.

sporte Tue, 03/08/2016 - 18:10

Tags

biotechnology

BLAST

Genetics & Molecular Biology

Sandra, that is fantastic, and you are doing great work. Your ideas need to go viral, so faculty in other universities can start doing likewise, pursuing this in whatever ways they can.

This can also be done for many of the other pressing issues of our time. Undergraduate education should include whatever work on real problems and real solutions is possible within the scope of the subject matter, in every field. If the kids are going to be learning basic principles whether they take that approach or the more conventional approach, there's no reason not to do it.

Thanks! I'm a firm believer in learning by doing but I'm not the only one.

The Vision and Change report and follow on articles by the National Science Foundation show there are many instructors that share the desire to have students use what they're learning and study problems they care about.

Zika: what we're still missing

tsmith — Mon, 01 Feb 2016 14:44:19 +0000

Zika: what we're still missing

As you've probably seen, unless you've been living in a cave, Zika virus is the infectious disease topic du jour. From an obscure virus to the newest scare, interest in the virus has skyrocketed just in the past few weeks:

I have a few pieces already on Zika, so I won't repeat myself here. The first is an introductory primer to the virus, answering the basic questions--what is it, where did it come from, what are its symptoms, why is it concerning? The second focuses on Zika's potential risk to pregnant women, and what is currently being advised for them.

I want to be clear, though--currently, we aren't 100% sure that Zika virus is causing microcephaly, the condition that is most concerning with this recent outbreak. The circumstantial evidence appears to be pretty strong, but we don't have good data on 1) how common microcephaly really was in Brazil (or other affected countries) prior to the outbreak. Microcephaly seems to have increased dramatically, but some of those cases are not confirmed, and others don't seem to be related to Zika; and if Zika really is causing microcephaly, 2) how Zika could be causing this, whether timing of the infection makes a difference, and whether women who are infected asymptomatically are at risk of medical problems in their developing fetuses.

The first question needs good epidemiological data for answers. This can be procured in a few ways. First, babies born with microcephaly, and their mothers, can be tested for Zika virus infection. This can be looked at a few ways: finding traces of the virus itself; finding antibodies to the virus (suggesting a past infection--but one can't know the exact timing of this); and asking about known infections during pregnancy. Each approach has advantages and limitations. Tracking the virus or its genetic material is a gold standard, but the virus may only be present in body fluids for a short time. So if you miss that window, a false negative could result. This could be coupled with serology, to look at past infection--but you can't be 100% certain in that case that the infection occurred during pregnancy--though with the apparently recent introduction of Zika into the Americas, it's likely that infection would be fairly recent.

Serology coupled with an infection in pregnancy that has symptoms consistent with Zika (headache, muscle/joint pain, rash, fever) would be a step up from this, but has some additional problems. Other viral infections can be similar in symptoms to Zika (dengue, chikungunya, even influenza if the patient is lacking a rash), so tests to rule those out should also be done. On the flip side, about 80% of Zika infections show no symptoms at all--so a woman could still have come into contact with the virus and have positive serology, but she wouldn't have any recollection of infection.

None of this is easy to carry out, but needs to be done in order to really establish with some level of certainty that Zika is the cause of microcephaly in this area. In the meantime, there are a few other possibilities to consider: that another virus (such as rubella) is circulating there. This is a known cause of multiple congenital issues, including microcephaly. This could explain why they're seeing cases of microcephaly in Brazil, but none have been reported thus far in Colombia. Another is that there is no real increase in microcephaly at all--that, for some reason, people have just recently started paying more attention to it, and associated it with the Zika outbreak in the area--what we call a surveillance bias.

This is a fast-moving story, and we probably won't have any solid answers to these questions for some time. In the interim, I think it's prudent to take this as a possibility, and raise awareness of the potential this virus *may* have on the developing fetus, so that women can take precautions as they're able. Public health is about prevention, and there have certainly been cases in the past of links between A and B that fell apart under further scrutiny. Zika/microcephaly may be one, but for now, it's an unfortunate case where "more research is needed" is about the best answer one can currently give.

tsmith Mon, 02/01/2016 - 09:44

Tags

I would be very interested in seeing epidemiological data from areas of where Zika virus has been known for decades. From the distribution maps I have seen, there are no "outbreaks" shown in continental Africa or Asia right now, but would outbreaks even be noticed? Does Zika "disappear" from circulation for substantial periods, or is it constantly in circulation but not really noticed? Given that most people infected will be asymptomatic and the symptoms in the rest are quite mild, it would seem that it could be "always around" but pretty much unnoticed.
If it is constantly in circulation, my off the cuff hypothesis is that the majority of girls would be infected and presumably develop reasonably good adaptive immunity well before they would bear children. If this were the case, then infection during pregnancy, along with any severe consequences to the fetus, would likely be rare.
Unfortunately, I suspect there is almost no data currently available.

Nice one! I have blogged on it on my site: rybicki.wordpress.com

Another possible explanation is industrial and agricultural pollution. The portion of Brazil reporting many cases of microcephaly is known for very high levels of pollution with toxic chemicals and heavy metals, compared to the countries that have numerous Zika cases but, as yet, no known increase in microcephaly. Brazil has had a nasty habit of letting those who speak against environmental destruction be murdered.

Excellent article on the Zika Virus. Unfortunately in Brazil, as long as the staff is not aware of it, to stop mosquito outbreaks, it will not end anytime soon.

Sara Lins by Sobre Microbiologia

Something scary for Halloween - polio virus

sporte — Wed, 28 Oct 2015 16:15:39 +0000

Something scary for Halloween - polio virus

When my parents were young, summer made cities a scary place for young families. My mother tells me children were often sent away from their homes to relatives in the country, if possible, and swimming pools were definitely off limits. The disease they feared, poliomyelitis, and the havoc it wrecked were the stuff of nightmares. Children could wake up with a headache and end up a few hours later, in an iron lung, struggling to breathe.

Poliovirus colored by molecule in Molecule World.

Today, on Jonas Salk's birthday, I read in the NPR blog Goats and Soda, that we're almost free of this scourge. The two scientists who developed vaccines against polio, Jonas Salk and Alfred Sabin, gave mankind the tools, and several others put them to good use. Be sure to check out Jason Beaubien's article and the amazing graphics showing poliovirus cases dropping across the world.

Since we have the luxury of distance, vaccines, and molecular modeling apps, we can explore the scary poliovirus from the safety of a phone or iPad. The way that I like to explore molecule models is to view a structure with different coloring styles and drawing styles and see if I can find patterns.

To explore poliovirus, I opened Molecule World** and downloaded structure 1XYR (Bubeck, et. al) from the Molecular Modeling Database (MMDB) at the NCBI. The 1XYR model is from a form the virus takes when it's about to enter a cell. It was obtained through cryo-electron microscopy.

In the first image, each protein in the poliovirus capsid is shown in a different color. The resolution isn't great, because electron microscopy can only do so much, so the structure model is built from the alpha carbon backbones of these 420 proteins.

In the image below, I changed the drawing style to tubes and applied secondary structure coloring to make the next image. Beta sheets are shown in orange and they make some interesting patterns on the surface of the capsid.

Poliovirus colored by secondary structure in Molecule World

I also found, when using a neutral color and spinning the capsized around that there appeared to be some kind of ring or pore in the structure. In the image below, I used a spacefill drawing style, colored by charge, and put the ring in the center. The amino acids around the "opening" are grey, showing they're uncharged. The images below that show beta sheets in the region around the ring and in residue coloring, the residue color key shows there are leucines, asparagine, and glycine.

Poliovirus colored by charge

Poliovirus drawn as spacefill, colored by secondary structure

I'm not sure what this pore or ring structure means for the virus, but for me, it means I'll have to read the paper and find out.

** I used the iPad version of Molecule World. I think Cn3D might work, too, but I had some problems. 1XYR can also be viewed with the Molecule World for iPhone, but the screen will be black when the structure is downloaded. Change the viewing mode to spacefill and you'll see the structure appear.

Reference:

Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The Structure of the Poliovirus 135S Cell Entry Intermediate at 10-Angstrom Resolution Reveals the Location of an Externalized Polypeptide That Binds to Membranes . Journal of Virology. 2005;79(12):7745-7755. doi:10.1128/JVI.79.12.7745-7755.2005.

Madej T, Lanczycki CJ, Zhang D, et al. MMDB and VAST+: tracking structural similarities between macromolecular complexes. Nucleic Acids Research. 2014;42(Database issue):D297-D303. doi:10.1093/nar/gkt1208.

sporte Wed, 10/28/2015 - 12:15

Tags

The World Health Organization says TB now rivals AIDS as the leading cause of death from infectious diseases.

Yes, that's correct, but as Laurie Garrett points out that many of the people who have TB, have it because of AIDS. https://twitter.com/Laurie_Garrett/status/659380176657235968

Ebola: Horror and Hope for a Cure

milhayser — Thu, 14 Aug 2014 13:08:56 +0000

Ebola: Horror and Hope for a Cure

As an unprecedented outbreak of Ebola crosses borders in West Africa, people are asking new questions about the virus and its potential to turn into a global pandemic (hint: it's not gonna happen). Greg Laden writes "The disease is too hot to not burn itself out, and it has no human reservoir. Ebola accidentally broke into the human population earlier this year or late last year." The current numbers from the WHO suggest 1800 confirmed and suspected cases of Ebola so far with a mortality rate edging down toward 55%.

Last week some in the U.S. objected to bringing two American patients back home, but Tara C. Smith writes that Ebola has been there all along, in government labs, while related viruses like Lassa and Marburg have been imported by infected travelers without causing additional cases. The one characteristic of Ebola we can be thankful for is that it is only spread through contact with bodily fluids, not through the air like a cold or flu. Smith concludes, "Ebola is exotic and its symptoms can be terrifying, but also much easier to contain by people who know their stuff." Meanwhile, Greg Laden writes that an extremely rare, untested 'cure' for the illness does exist, and it has also been given to the two infected Americans. He's referring to anti-serum, i.e. blood serum containing natural Ebola antibodies modelled after those generated by infected mice. On Discovering Biology in a Digital World, Sandra Porter shows how the antibodies lock onto viral proteins, and says it is time to focus on mass-producing an effective antiserum for this horrible disease. On ERV, Abbie Smith explains how the manufacturing process works: genetically modifying viruses to contain blueprints for parts of Ebola antibodies, putting the viruses in bacteria as delivery vehicles, and using the bacteria to infect GMO tobacco plants whose cellular machinery will be hijacked to make molecules. Smith writes, "Plants are a pretty cheap way to produce a lot of protein. Blow up the plant cells, purify your protein, and BAM! A ton of anti-Ebola antibodies."

milhayser Thu, 08/14/2014 - 09:08

Tags

One point has not yet been made clear in the coverage of Ebola that I have seen: does infection confer immunity on survivors? If Dr. Brantly chose to return to Africa, would he be safe from reinfection?

If Ebola works like smallpox did, there would be significant implications for controlling the disease; immune survivors would be able to work directly with sick patients without fear of contracting the disease themselves. They could dispense with the personal protective equipment that can frighten patients and deter them from presenting for treatment. Such equipment is a scarce resource in Africa, and survivors with even rudimentary training as caregivers could contribute to the control of the spread of the disease.

On antiserum and Ebola virus

sporte — Sun, 03 Aug 2014 22:24:22 +0000

On antiserum and Ebola virus

In 1925, dogsledders raced through the frozen Alaskan bush to bring antiserum to the isolated village of Nome. The antiserum arrived in time, saved the lives of many villagers from the horrors of diphtheria, and inspired the Iditarod, a famous race in celebration of the dog sledders' heroic feat.

West Africa could use a similar effort today. Richard Harris's blog at NPR has a good story about doctors' efforts to develop and use antiserum to treat Ebola. According to ABC news, Dr. Kent Brantly, who is being seen at Emory University Hospital was treated with antiserum as was the other aid worker, Nancy Writebol.

Antiserum is the liquid portion of blood that contains the antibody proteins. Antibodies are present in your blood all the time, but special cells, the B cells, produce more of them when your body is trying to fight off some kind of disease. The problem is that it takes time for your body to make these proteins and even then, the proteins you make might not work very well.

When immediate protection is needed, antiserum can act much more quickly. That's why we use antiserum to treat cases of snake bite, hepatitis exposure, and to protect people from tetanus. And that's why it was important for stopping diphtheria and saving the children in Nome.

I thought you might like to see a close up view of what these kinds of antibodies look like.

This image is from a structure I downloaded from the NCBI, 3CSY, and viewed in Molecule World. It shows a portion of an antibody, called the Fab fragment, bound to two of the glycoproteins from the outside of the Ebola virus. The antibodies were derived from someone who was infected with Ebola in the 1995 Kikwit outbreak and survived (1).

Zooming in lets me see how tightly the antibody and the viral proteins fit together.

We can see where the antibody binds to the viral protein, right near some of the sugar residues. Knowing the amino acid sequence at the antibody binding site can help scientists engineer protective antibodies and produce them in E. coli or other other organisms. These kinds of treatments aren't perfect, but they can help Ebola victims.

I made all the pictures from images saved in Molecule World.

Reference:
Lee JE, Fusco ML, Hessell AJ, Oswald WB, Burton DR, & Saphire EO (2008). Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature, 454 (7201), 177-82 PMID: 18615077

sporte Sun, 08/03/2014 - 18:24

Tags

So If the serum is effective why aren't they using it more?

Great question! Maybe if there were larger amounts available they would.

Isn't there also a non-zero danger of transmitting other diseases through serum? I mean, it's a heck of a thing to save someone from Ebola only to give them HIV, or syphilis, or HepC. So you have to screen donors that are known to have survived Ebola *and* are free of serious bloodborne pathogens. And that might be a pretty small pool of people, and then you have to find the willing ones.

Also, are there risks of immune response to other material in the serum, or is it clean enough you don't have to worry about blood type and MHC matching?

@JustaTech: you're absolutely right. Other diseases like HIV and hepatitis B can certainly be transmitted through serum.

A better way to deliver passive immunity is probably to purify the antibodies from the serum. We can also make antibodies in other animals, like horses, and use those antibodies to provide passive immunity. This is done in the case of snake bite anti-toxin and I think tetanus anti-toxin, too.

Providing passive immunity through antibodies isn't a perfect treatment. As you noted, people can develop an immune response to antibodies and this can have severe consequences. However, the technology for engineering antibodies has improved greatly over the past years and I think people have been able to change the sequences and make them less likely to trigger an immune response.

Interestingly, I learned just recently about a biotech company that's manufacturing antibodies in tobacco plants. This seems pretty promising. Now, the challenge is to figure out how best to resolve the questions of safety and access.

It's not easy to choose between the prospects of conducting experiments on desperate people or letting the disease follow it's natural course.

Viruses are usually intracellular and antibodies are ineffective. A cell mediated response is necessary to kill the infected cell. They might bind circulating virus and reduce total load, but won't be able to kill intracellular virus.

Cellular immunity is an important mechanism for defense, but antibodies can be important, too.

In the image that I posted above, the antibodies are binding to a protein that would be found on the outside of a viral particle. These kinds of antibodies can help in the immune response by blocking viruses from entering a cell.

Here's a great article on this and it's open access:

Antibody-mediated Neutralization of Ebola Virus Can Occur by Two Distinct Mechanisms
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351102/

Undead Science

milhayser — Tue, 12 Nov 2013 12:20:46 +0000

Undead Science

On Aetiology, Tara C. Smith continues her series on the science of The Walking Dead, explaining how diseases spread and how they might cause zombiism. One thing that would be observed in any real contagion would be an incubation period— the time between when a virus (for example) enters your body and you start showing symptoms of infection. For a virus like the flu, this could be about two days during which you don’t feel sick but could still be infecting people around you—even if you don’t bite them. Tara also expresses nerd rage at the show's "doctors" pursuing antibiotics to treat the flu, since antibiotics kill bacteria, not viruses. On ERV, Abbie Smith presents interesting data on infectious killers in North America, both vanquished and ongoing. The last case of Smallpox was documented in 1977. But flu bugs, which live in “reservoirs” in other animal species, mutate all the time, and some years' flus are deadlier than others.

For Halloween, Chad Orzel explained how to base a sexy costume on a bunch of nerdy white guys, such as Niels Bohr: “a little Brylcreem, a soccer ball, and a lot of mumbling and equivocation, and you’re good to go.” On Pharyngula, PZ Myers wondered if Antonie van Leeuwenhoek is thirsting for cheap technology is the grave, like a do-it-yourself photomicrography setup that lets you take pictures of wee beasties with your smartphone. And Ethan Seigel pulls us back from the whole death-and-decay thing with his latest costume: Rainbow Dash from the cartoon My Little Pony: Friendship is Magic.

milhayser Tue, 11/12/2013 - 07:20

Tags

Can we "catch" breast cancer?

tsmith — Wed, 27 Feb 2013 08:00:39 +0000

Can we "catch" breast cancer?

Third of five student guest posts by Dana Lowry

In 1911, Peyton Rous first discovered viruses can cause cancer. A chicken with a lump in her breast had been brought to Rous by a farmer. Rous prepared an extract that eliminated bacteria and tumor cells and injected this extract into other chickens—tumors grew. Rous suggested “a minute parasitic organism” was causing the tumor growth, which is now known to be a virus. However, Rous’ discovery remained very controversial, and it wasn’t until 1966 that he was awarded a Nobel Prize for his discovery. Since Rous’s discovery, researchers have found an estimated 15 percent of all cancers worldwide are associated with viruses. Some common virus and cancer associations are: human papilloma virus (HPV) and cervical cancer, hepatitis B and liver cancer and human T lymphotropic virus type 1 (HTLV-1) and T-cell leukemia.

Epstein-Barr virus (EBV), a member of the herpesvirus family, is one of the most common viruses worldwide. Among 35 to 40 year olds in the U.S., up to 95% have been infected with EBV. Oftentimes, children infected with EBV have no clinical signs or symptoms; however, 30% to 50% of adolescents and young adults exposed to EBV for the first time will develop infectious mononucleosis, commonly known as mono. In the U.S., individuals are usually exposed to EBV in adolescence or young adulthood compared to developing countries, where oftentimes individuals are exposed as infants or young children. EBV usually remains dormant in the body throughout an individual’s lifetime, similar to the varicella-zoster virus, the virus responsible for the chicken pox. EBV is known to play a role in Burkitt ’s lymphoma (cancer of the immune cells), nasopharyngeal cancer (cancer of the upper throat) and Hodgkin’s lymphoma (cancer of the lymphatic system), but can EBV also play a role in breast cancer?

In 2010, James Lawson and Benjamin Heng reviewed 27 papers concerning EBV and breast cancer associations. EBV infections are universal in high and low risk breast cancer groups, making it unlikely that EBV is the sole contributor to forms of breast cancer [1]. However, the age at which EBV is contracted seems to play a role in the risk of developing breast cancer. Women in Western countries are at higher risk of developing breast cancer and tend to be infected with EBV during adolescence or young adulthood, whereas women from non-Western countries have a lower risk for developing breast cancer and tend be infected during infancy or early childhood. Hodgkin’s lymphoma shares a similar correlation with higher rates in Western countries [2]. Although there seems to be a relationship between age of EBV infections and risk of breast cancer, potential confounders need to be considered. Women in developing countries tend to have more children, have children at a younger age and breastfeed their children for longer periods of time. Breastfeeding, having more children and having children earlier in life all seem to be protective factors against breast cancer.

Beyond epidemiological evidence, lies biological evidence. Twenty two of the studies Lawson and Heng reviewed were based on polymerase chain reaction (PCR) techniques. Issues have been found with standard PCR procedures, but it is becoming widely accepted that EBV can be identified in breast cancer tissue through specific PCR techniques [1]. EBV genes have been found in breast cancers through polymerase chain reaction (PCR) analyses. EBV has not only been shown to shed in human breast milk [3], but it has also been shown to stimulate growth of human breast-milk cells [4]. The mechanism by which EBV actually causes cell alterations is not known, but it is thought to be different from the mechanisms used in lymphomas and nasopharyngeal cancer [1].

It is unlikely that we can actually “catch” breast cancer, as EBV doesn’t seem to be the sole cause of breast cancer. EBV may contribute to breast cancer by altering genes in the breast cells which eventually leads the uncontrolled cell division, known as cancer. More importantly, it seems the age an individual is infected with EBV may play an even bigger role in the outcome of disease. An EBV vaccination is in the works that will hopefully prevent infectious mononucleosis and EBV-associated cancers. However, the vaccination may not prevent the EBV infection itself; it is targeted towards the most abundant protein on the virus and on virus-infected cells. If the vaccination proves to be successful, it will be interesting to see if a reduction in breast cancer rates will follow, along with the known cancers associated with EBV. Only time will tell.

References:

Lawson, J. and Heng, B. (2010). Viruses and Breast Cancer. Cancers 2010, 2(2), 752-772; doi: 10.3390/cancers2020752.

Yasui et al. (2001). Breast cancer risk and “delayed” primary Epstein-Barr virus infection. Cancer Epidemiology, Biomarkers & Prevention, 10:9-16. http://cebp.aacrjournals.org/content/ 10/1/9.long.

Junker et al. Epstein-Barr virus shedding in breast milk. (1991). The American Journal of the Medical Sciences, 302: 220–223. http://www.ncbi.nlm.nih.gov/pubmed/1656752.

Xue et al. (2003). Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger?. British Journal of Cancer, 89:113–119. http://www.nature.com/bjc/journal/ v89/n1/full/6601027a.html

tsmith Wed, 02/27/2013 - 03:00

Tags

Cancer epidemiology

Infectious causes of chronic disease

Outmaneuvering Influenza

milhayser — Fri, 18 Jan 2013 08:57:01 +0000

Outmaneuvering Influenza

Flu season is gearing up in the northern hemisphere, and this year's strains appear more virulent than usual. In the United States, the Centers for Disease Control declared an epidemic on January 11; the CDC estimates that between 3,000 and 49,000 people die from influenza or its complications every year. By comparison, the infamous flu of 1918 may have killed 500,000 Americans. Although the very young, elderly, and diseased bear the highest risk of death, healthy adults still bear the responsibility of minimizing overall transmission of the virus. In other words, everyone should get vaccinated. On ERV, Abbie Smith writes that the influenza virus is highly mutable, and we must devise a fresh vaccine every year in anticipation of its new forms. This year's vaccine has an efficacy of 62%, better than average. Meanwhile, on We Beasties, Kevin Bonham explains what happens when you are infected by more than one pathogen at a time.

milhayser Fri, 01/18/2013 - 03:57

Tags

influenza

viruses

AskScience: Is it possible to get multiple different colds/flu viruses at the same time?

kbonham — Tue, 15 Jan 2013 09:00:21 +0000

AskScience: Is it possible to get multiple different colds/flu viruses at the same time?

There are a lot of reasons that posts to this blog sometimes don't happen for months at a time, but one of them is that I can often get sucked down the rabbit hole that is Reddit. If you don't know about reddit yet, you may not want to click that link, but if you do know (and you're reading this blog), you may know about one of the communities (subreddits) there - a place called r/askscience. It's a forum where people can ask questions of a scientific nature (anything from "Why are pigeons so successful as an urban animal?" to "What's so special about the speed of light?"), and then actual scientists from a slough of different fields will answer. I'm a panelist (one of those scientists), in this community, and I've spent a lot of time answering questions there, so I thought I'd let that work do some double-duty here. I'll start with some questions that I answered a while ago, but I'll try to post future responses in a bit more timely matter. If you have any questions you'd like to ask, please do!

Question: Is it possible to get multiple different colds/flu viruses at the same time? If so, what are the effects?

Answer:

Yes, this is called a "superinfection."

The effects will vary quite a bit depending on the details. Many of the responses of the immune system to an infection are general - if you get infected with two rhinoviruses (one of the virus types that causes "colds") of the same type or two rhinoviruses of different types, the cells around the area of infection will respond in essentially the same way - principally by activating inflammation and something called the "antiviral state."

The response of your adaptive immune system (T-cells and B-cells) will be a bit different, since there would be two sets of activating signals with a co-infection, but it's hard to max out an immune response, and to some extent the different viruses will be competing with each other. It's possible that it will take you longer to recover, but I'm not aware of any solid data on this.

On the other hand, if you are co-infected with two different types of infection, say a bacterial and a viral infection, this can cause serious problems, since the immune response necessary to deal with viruses and the response necessary to deal with bacteria can be quite different, and the response to one can be counterproductive to the response to the other. In fact, most people that die "of the flu" actually die from bacterial infections of the lung that were able to gain a foothold because of the immune response to the flu virus.

Follow-up question: Would having a fungal infection of say... of the skin decrease the effectiveness of the immune systems ability to fight a bacterial and or viral infection at the same time?

Answer:

A fungal infection in the skin is not likely to effect the immune response in, say the lung. Again, it depends a lot on specifics, and some infections can have systemic consequences. But as I said before, it's hard to run out of immune response. The reason that having two different kinds of infections in the lungs is an issue is not because you're running out of immune response, but because the immune environment is different.

Think about it this way - say you're the military and you're trying to combat an invading army and also rescue hostages being held by terrorists. If the invasion is in Boston and the terrorists are in New York - no problem. You can bomb the army and send in SWAT for the terrorists. If the terrorists are in a building surrounded by the invading army, then getting SWAT into the building is going to be impossible, and bombing the army is going to kill your hostages. Different immune responses are necessary to combat different types of infections, and they're not always mutually compatible. But if the infections are in different places, the immune system is more than capable of local responses.

kbonham Tue, 01/15/2013 - 04:00

Tags