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TWiV 132 Letters

Maki writes:

To the hosts of TWiV (I find the fact that you're called "hosts" of a virology-centered show endlessly amusing.):

Having been the weird kid reading Virus Hunters on the playground in elementary school, I've had an intense love for virology and epidemiology for as long as I can remember. Fast forward a decade and I find myself as a post-bac research tech with my mind drifting toward the possibility of grad school. I've been trying to study on my own in order to focus my brain toward a future of classroom education, but after a demanding day of trying to keep up with advanced-degree level work, it's hard to crack open a textbook and read about singledoublestrandDNARNAblahblah without my eyes glazing over. Let's not even get into what happens while reading journals.

I just discovered your podcast last week and since, it's been a constant source of entertainment (oh yes, I consider it the height of entertainment) during transit and the rote tasks of my day. I want to sincerely thank you for the work you do. I'm eager to listen to the rest of TWiV/ TWiM/ TWiP and I know that you're going to be great for the advancement of my education. (Heck, you already have been with the first ten podcasts!)

Every day that I arrive at work after listening to you, I feel inspired by the possibilities of research, which can be so demoralizing some days, and ready to throw myself into my own current research, despite it not being in my field of choice. Again, thank you so much. Your insight and knowledge are very, very much appreciated, as is your patience with my verbosity if you've made it this far down.



The Scripps Research Institute

San Diego, CA

John writes:

Dear TWIVers,

I was just listening to TWIV 122, and this made me think of two somewhat related questions.

First, you discussed a gene involved in innate immunity inside the cell (TRIM-5 alpha), which provides a natural defense against retroviruses, and which has some alleles that have been preserved, more-or-less, across species that diverged millions of years ago. You talked about a bunch of possible explanations, but one you didn't discuss involved endogenous retroviruses. I am curious if that could explain the preservation of some of these alleles in primates. (I should point out I'm not a biologist, but a computer scientist. So I may be misunderstanding things here.)

The way I imagine this working is that there's a population of ERVs hiding out in the genes of different species of primates, Some ERVs reawaken pretty regularly, so that in the average individual, it's not surprising to have the ERV showing up. In those species, the allele of TRIM-5 alpha that protects against them will be really common, because it provides a big fitness advantage. But it seems like there should also be some ERVs that reawaken only much more rarely--perhaps they need a helpful mutation, or some really unlikely sequence of events inside the cell, before they can come back out. And those would support balancing selection between alleles--if you have some ERV that only comes out once per generation, the value of an allele that resists it is based on how common that allele is in the population. If almost everyone else has it, you hardly need it--most likely, the retrovirus will never spread to you, and you're not at all likely to be the one individual per generation in which the ERV reawakens. The more rare that allele becomes in the population, the higher its fitness value to an individual, and so the more it is selected for--once-per-generation epidemics of some nasty retrovirus should keep some level of the resistance allele in the population. The more rare the events that allow the ERV to come back to life and start spreading again, the more rare you'd expect the allele that provides resistance to it to become, but it seems like that should still keep some level of the allele around. Imagine a once-per-twenty-generations epidemic of something as nasty as HIV sweeping though your population. When that epidemic comes out, the fraction of the population carrying the allele that gives resistance to it will very quickly jump from a small fraction to nearly everyone.

My question is, could this account for some of the preservation of these TRIM-5 alpha alleles across long-separated species? As long as you have the same (or similar) ERV reawakening from time to time in two distant lineages of monkeys, it makes sense you'd have the same (or similar) alleles to provide resistance to that ERV. But this assumes that the ERVs can stick around that long in forms that can replicate under the right circumstances. (It seems like the ERVs could stick around by managing to re-insert themselves into the germline when they manage to come out and trigger another epidemic, after most of the population had lost its resistance.)

Is this at all plausible? The more time I spend writing this out, the more assumptions I find I'm making that I don't know enough to confirm. That's the problem with speculating far outside your area of expertise, I guess.

My second question involves a book I want to recommend as a pick of the week, if you haven't already chosen it. It's a book published in 1949 called _Earth Abides_, by George R Stewart, in which a sudden epidemic of some unknown thing nearly wipes out the human race, with perhaps one person in a thousand surviving. Reading this around the same time I listened to your discussion in TWIV 122 made me wonder how likely it is that some epidemic could arise that kills that large a fraction of humanity. I know the original population of American Indians was nearly wiped out by disease, though I think it was multiple diseases--Measles, mumps, chicken pox, influenza, smallpox, the whole package all at once. How common is it that a single disease kills 99% of the people who get it, and also spreads easily?

This made me think of HIV, because it's always seemed to me that if HIV had been spread by casual contact, it would have killed off most of humanity. (The several-year incubation period before it becomes lethal would have kept us from noticing it--who noticed one more flu bug going through the gay communitiy in San Francisco, till people started dying from it years later?) I know there's some fraction of people that don't get it (they have a variant coreceptor that keeps the virus from entering, right?) and others that catch the virus but seem to control it indefinitely (from having the right set of MHC molecules to be able to recognize all the HIV mutations that arise in their bodies, I think). Is there a good figure for what fraction of people, total, don't die of HIV? How common is it historically to see one disease nearly wipe out a whole population?

Thanks for your wonderful podcasts, and for answering my amateur questions.


James writes:

Hey Doctors,

After reading this article I immediately thought of TWIV. Now It looks like there is hope to combine my field of cytogenetics with your field of virology.

Keep up the great work. I look forward every Monday for a new episode.


Northwestern Memorial Hospital

Human Genetics Laboratory

Cytogenetic Technologist

Shammah writes:

I found your podcast while browsing thru iTunes and i have to say i'm hooked. I have the most boring job but i get to listen to my MP3 player. I have nothing to do with the medical field so some of the stuff is way over my head but it's fun to learn about viruses, especially the freaky ones. I was wondering if there have been any studies looking at HIV, generic drugs, and resistance; specifically if generic drugs lead to resistance faster. While the FDA and drug manufactures say generic and name brand are bio-equivalent, I have my doubts. I take Zyrtec for allergies and have tried every store brand i could but within 3 days I'm feeling horrible and have to switch back to the expensive, name brand. Since they generic seem not to work for me, I was wondering if the same could be true for generic HIV drugs. While there are only a few generics in the US, third world countries count on them to keep costs low. Thanks and thank you for a wonderful podcast.


Sarah writes:

I would totally buy a TWiV T-shirt, mug, or tote bag that said "Does a virus shift in the woods?"




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