Intro to ERVs: Quick point about retroviruses

Before I start talking about endogenous retroviruses, there is one thing I need to make clear about exogenous retroviruses first, for anyone who deals with pseudoscientists.

When dealing with Creationists/Deniers on the topic of virology, almost immediately you will be confronted with a form of ‘viruses are magic’. For instance, Professional HIV Denier Rebecca ‘Blondie’ Culshaw is just certain that HIV-1 is really a harmless ERV (see points 1-17), and Creationists routinely pull ‘scientific facts’ about ERVs out of thin air.

So I really cant stress this one point enough:

Okay, you all know that a retroviruses are viruses that go ‘backwards’, genetically. Instead of going DNA–>RNA–>Protein, they go RNA–>DNA–>RNA–>Protein. While its easy to lump all ‘retroviruses’ into a homogeneous group, its important to remember that retroviruses are actually an extremely diverse family.

To say ‘HIV-1 is the same as Rouse Sarcoma Virus is the same as Mouse Mammary Tumor Virus. Theyre all retroviruses!’ is as silly as saying ‘Humans are the same as blue whales are the same as fruit bats. Theyre all mammals!’

There are currently seven types of retroviruses, with their own defining genes (simple? complex? lots of bells and whistles?), methods of virus assembly (cytoplasm? cell surface? trafficked through the ER?), viral structure (cone? cylinder? sphere? spikes? sugars?), desired host cells (dividing cells? terminally differentiated?), etc.

But what all of these guys have in common is their need for the genes gag, pol, and env (which I will be discussing more at a later date), genes we can sometimes find hanging out in our DNA as endogenous retroviruses:

Alpharetroviruses– Can be ERVs
Betaretrviruses– Most ERVs
Gammaretroviruses– Can be ERVs
Deltaretroviruses– No ERVs
Epsilonviruses– No ERVs
Lentiviruses– We have found *one* lentiviral ERV
Spumaviruses– Can be ERVs, but the endogenous versions are only distantly related to current-day, exogenous spumaviruses

So in future posts when Im talking about ERVs, or when you are dealing with a pseudoscientist talking about ERVs, remember we arent just playing Bible-code games. We know what group the ERV in question used to belong to. We can trace how that ERV mutated differentially in different species of primates, or notice its only found in humans, or that its only found in chickens. We can know the ERV in question isnt coding for HIV-1.

If your pseudoscientist friend says something that sounds like magic– “Well maybe HIV-1 is an ERV that got a functional envelope gene from influenza cause you had the flu and were huffing poppers!”– Dont stand for it. Say “Retroviruses are not magic. Show me the evidence for that claim.”

And, if you want to learn more about retroviruses (I mean beyond Wikipedia, but not quit ‘IM GONNA GO BUY A TEXTBOOK!’), Cold Spring Harbor has a book on retroviruses online, for free!! Its ‘advanced’ reading, but if this topic interests you, you can get through it. Or if you get stuck, leave me a Q in the comments or drop me an email

Comments

#1 Paul Lundgren
May 12, 2008

Abbie, I just want to thank you for this post. Not because I understand a word of it, because I don’t. But because it’s obvious there are still smart, optimistic, devoted, and determined people in the world who will strive to make a difference. Thank you.
#2 ERV
May 12, 2008

NOOOOOOOOOOOOOOOOO!!!!

NOOOOOOOOOOOOOOOOOOOOOO!!! Dont say that!!!

If you dont understand something, ask a Q!!! Because if YOU have a Q, that means someone else probably has the same question, which means I need more practice talking about this stuff cause EVERYONE can get this stuff!!!

Ask questions!
#3 Joshua Zelinsky
May 12, 2008

Ah dammit, now I have another book to read. And this one is free too so it is even harder to resist. I should just avoid all the interesting blogs. I’d get so much more done that way.
#4 Jason Creighton
May 12, 2008

Sorry, this isn’t strictly related to this post, but it’s something I was wondering about and couldn’t find the answer to: This video by cdk007 says (at 5:45) that there are 16 ERVs in common between humans and chimpanzees and then goes on to clarify (at 6:45) that those are “K class retroviruses” and that there are ~98,000 ERVs total in the human genome.

My question is, what is a K class retrovirus, and why are there so few (16 in common with our closest related species) of them compared to other types of ERVs?
#5 Shirakawasuna
May 13, 2008

“To say ‘HIV-1 is the same as Rouse Sarcoma Virus is the same as Mouse Mammary Tumor Virus. Theyre all retroviruses!’ is as silly as saying ‘Humans are the same as blue whales are the same as fruit bats. Theyre all mammals!’”

I have to admit I don’t know a ton about retrovirus phylogeny, but given my ignorance couldn’t it be more accurate to say that it’s like pointing out that bees, chickens, and coral all have pointy protrusions, so they’re all the same? I ask this because if these defining characteristics of retroviruses do not correlate with a single monophyletic group (outside going back really, really ridiculously far), couldn’t they be an analagous character rather than homologous?

Of course, this is based entirely on my speculation and ignorance, so I’d appreciate any correction!
#6 Confused
May 13, 2008

Which of the seven is HIV, out of curiosity?
#7 Stephen Wells
May 13, 2008

IIRC HIV is a lentivirus, which means “Kills you reeeeal slow.”
#8 Joshua Zelinsky
May 13, 2008

HIV is a lentivirus.

See http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_retro.htm#Genus16
#9 ERV
May 13, 2008

@ #4

Thats a neat video! They got a little confused, but not much– When he/she said ‘K class of retroviruses’, they meant the HERV-K family of endogenous retroviruses!

When scientists started hunting for families of ERVs in Humans (HERVs), they started at the beginning of the alphabet, and moved down: HERV-A, HERV-B, HERV-C, etc.

HERV-Ks turned out to be a neat family, because they happen to be the ‘youngest’, thus most intact, thus most capable of forming viral particles. Because theyre so young, its possible that HERV-K 1 is found in humans only, while HERV-K 2 is found in both humans and chimpanzees, meaning following the HERV-K family insertion pattern is a great way to tease out primate phylogenies
#10 ERV
May 13, 2008

PS– Search for ‘HERV-K chimpanzee’ for lots of cool info
#11 Fleming
May 14, 2008

Umm, Do retroviruses have any clinical relevance whatsoever?

Top ten killers in USA per CDC:

Heart disease: 652,091
Cancer: 559,312
Stroke: 143,579
Chronic lower respiratory diseases: 130,933
Accidents: 117,809
Diabetes: 75,119
Alzheimer’s disease: 71,599
Influenza/Pneumonia: 63,001
Nephritis, nephrotic syndrome, and nephrosis: 43,901
Septicemia: 34,136

Do you see any retroviruses on this list? Do you now understand why you toil away at 10 bucks/hour? Your work has not an iota of relevance to the real world.
#12 aporeticus
May 14, 2008

Do you see any retroviruses on this list?

uhh
#13 Brian
May 14, 2008

Wow. My work also doesn’t help alleviate any of the killers on Fleming’s list. I guess my job also has not an iota of relevance to the real world.
#14 Rrr
May 14, 2008

Wow. My work also doesn’t help alleviate any of the killers on Fleming’s list. I guess my job also has not an iota of relevance to the real world.

Ignore him. He is just Flaming and can’t even spell.
#15 trrll
May 14, 2008

Do you see any retroviruses on this list? Do you now understand why you toil away at 10 bucks/hour? Your work has not an iota of relevance to the real world.

This is a really stupid comment in a number of ways.

To begin with ERV is a graduate student. Graduate students get paid a bare survival wage, in part because they aren’t yet worth a lot, and in part because most of their benefit is in the training they receive. And it doesn’t matter whether they are working on some obscure protein that nobody knows what it does or on heart disease. Graduate students at an institution generally all get paid pretty much the same (barely enough to survive).

It is also an example of the “bigger problem” fallacy: “You shouldn’t be worrying about X, because Y is a much bigger problem!” This is a really, really stupid way to think. Taking this reasoning to its logical conclusion, there is one “biggest problem,” and nobody should work on anything else until it is solved. In reality, scientific requires diversity, just like an ecosystem. Throwing all of your effort at the “biggest problem” doesn’t necessarily get it solved any faster; at any given time, there are only so many good ideas and approaches, so you get to a point of duplication of effort and diminishing returns.

Moreover, in basic research, it is sometimes not the direct attack that yields the solution to a problem. Very often, it comes from something discovered by some other guy who was working on some obscure question that nobody thought was very important.

Finally, research needs to be dedicated not merely to the present, but to the future. The fact is that we really don’t understand viruses very well, and viral infections are really hard to treat, because viruses have only a few proteins of their own, and mostly hijack the cell’s apparatus. HIV was a big wakeup call. We were very, very lucky that HIV is so difficult to catch that you pretty much have to have sex or share blood to get it. The next virus to come down the pike might not be so well-behaved. But HIV got us worrying about viruses, so now if we run into a really nasty one, maybe we’ll be prepared.
#16 themadlolscientist
May 14, 2008

Instead of going DNA–>RNA–>Protein, they go RNA–>DNA–>RNA–>Protein.

=lightbulb suddenly switches on= Yeah, now I get it!

(Bet you couldn’t tell that biology isn’t my usual stomping ground, huh? No, really!)

Thanks for the clearest, most concise explanation I’ve ever seen regarding retroviruses. I had a vague idea what they’re about, but the name “retrovirus” still conjures up the weird idea of a virus that somehow infects you before you’re exposed to it. Never mind that I know full well that [1] no such thing exists and [2] the very idea is ridiculous.

Maybe I’ve been warped by reading too much Asimov in my younger daze…….
#17 penguindreams
May 14, 2008

Nice note Abbie.

Your troll, #11 here, is, well, typical for that species. Like most, it goes ahead and uses the results of science that would never have existed if he had his way. It’s true that some important things were found by people who were trying to find them. So it can keep the smallpox vaccine and the steam engine.

On the other hand, it has to give up penecillin and anything that uses electricity, among many other things. Alexander Fleming was not trying to find antibiotics when he discovered penecillin. And electricity spent over 2 centuries as a highly abstract bit of science (starting from, let’s say, Oersted in the 1600s and up to mid-1800s).

Also have to give up anything that uses radio waves (granted that’s already eliminated by the fact the troll can’t use electricity) as their existence was a theoretical prediction out of Maxwell’s equations, themselves developed for no particular application. Just trying to understand the universe.
#18 ck1
March 11, 2009

From one retrovirologist to another, thanks for the clear post!

One nitpick, though. In your post #9 you state that the HERVs were named alphabetically. Actually the letter designations refer to the fact that different HERVs use different tRNAs as primers. HERV-K uses lysine, letter symbol = K. Etc.

This nomenclature system is not so meaningful as more and more HERVs have been discovered.
#19 ERV
March 11, 2009

Yup. I totally screwed that one up I confessed my sins the last time I was on BloggingHeads, and I forgot to come back to fix that comment! Thanks for finding it for me
#20 ck1
March 11, 2009

To poster #11:

In addition to HIV, retroviruses HTLV-1 and HTLV-2 cause human disease. Also, mouse-related gammaretroviruses have been isolated from human prostate cancers.

Retroviruses also cause disease in economically important species, like sheep and cats and chickens.

Finally, retroviruses are known to jump species. In addition to HIV-1 and the prostate example given above, mouse-related gammaretroviruses have also been found in koalas and gibbon apes where they have generated ERVs.
#21 Aaron
October 3, 2010

Can you provide some examples of modern exogenous betaretroviruses that infect primates? The only examples I saw infect sheep and mice. Did we inherit our endogenous betaretroviruses from them?

A quick wiki search indicates that the exogenous forms of the other ERV branches that you mention typically cause types of cancer or leukemia or immune deficiency.

Can you explain how a developing embryo (much less a newborn) is able to survive if he/she has even one of these retroviruses within each and every cell? (I’m speaking in terms of when that retrovirus first becomes endogenous through an infected sperm – not the mutated forms we have throughout our genome).
#22 W. Kevin Vicklund
October 4, 2010

One such example is Mason-Pfizer monkey virus (M-PMV), originally isolated from rhesus monkeys. Search hint: it is not necessary to include ‘exogenous’ in the search criteria, although specifically excluding ‘endogenous’ will help cut false positives.
#23 Aaron
October 5, 2010

Thanks Mr. Vicklund.

In order for an ERV to infect a germ cell and not destroy it or the zygote, would you assume that:
a) the retrovirus was not virulent to begin with?
b) the retrovirus experienced a mutation after inserting into a spermatagonia – thus leaving the progeny sperm with a defective – non viral producing provirus?

However, even if the retrovirus was not virulent, wouldn’t it eventually kill the host cell when the newly created viruses escape from the cell?
And wouldn’t this be happening in every cell of the baby’s body?

Any thoughts?
#24 W. Kevin Vicklund
October 6, 2010

Those are two possibilities, but are not exhaustive. Other possibilities include, but are not limited to:

c) the cell has suppressed expression of the ERV
d) the virus doesn’t need to kill the cell to reproduce (google ‘viral shedding’) or does so slowly
e) the virus is latent and needs a particular stimulus to start up again
#25 Aaron
October 7, 2010

Thanks again.

c) How would the cell do this? Methylation of the ERV provirus? (but wouldn’t that take a while?) I read about cytidine deaminases like APOBEC3G – which seem to be the cell’s primary defense against retroviruses. However, APOBEC3G is limited to when the virus enters the cell – prohibiting the virus from ever inserting its DNA into the host genome. So, it doesn’t seem feasible that such a deaminase defense would work in the developing fetus because the DNA would already be in place – and without the initial viral break-in, the cell wouldn’t be alerted to the need of utilizing APOBEC3G. The provirus would already be accepted as a “normal” part of the host genome.

d)If I understand correctly, all known retroviruses leave the cell through budding. While this seems to be the least harmful to the cell initially, wiki says “This process will slowly use up the cell membrane and eventually lead to the demise of the cell.” So, slow or quick, this type of virus reproduction would still kill the cell. Again, with a newly endogenous retrovirus, this would be happening in every cell of the fetus’ body. Still not sure how it would survive this…

e)Correct me if I’m wrong, but aren’t viruses only able to remain latent in non-diving cells? This certainly isn’t the case in a developing fetus – all of the cells are dividing. Even when the baby is fully formed and the non-dividing cells are established – the ERV is still in every cell of the body, including the most rapidly dividing cells. I don’t see how a freshly endogenous virus has the luxury of remaining latent.

I’m only pressing these points because I’d really like to understand all this more.
#26 Aaron
October 12, 2010

Any help from the experts?….