TWiV 263 letters

Ian  writes:

Dear Twiv team,

greetings from a rather dark and damp Cambridge.

Firstly I wanted to pass on my congratulations on such a fantastic resource for the virology community. I listen to TWIV every day on my 15 minute cycle to and from work and I particularly like the rather ‘casual’ approach – whilst other listeners may have commented that you could cover the same amount of material in half the time, I like the feeling that I am simply listening in to a conversation between friends in a bar. My only criticism is that it doesn’t last long enough for my weekly commuting, after 3 days I find myself having to listen to TWiM, not necessarily a bad thing as I have learnt a lot.

So the reason for my email. I enjoyed listening to the episode on the principles of virology (TWiV 245), always nice to hear how these things evolve in a very non-linear way. I wanted to highlight one mechanism of viral translation that appears not to be covered in the book and was also not mentioned during your recent episode on viral translation (Lost in Translation TWiV 238), namely VPg-dependent translation. There are several families of viruses that appear to have a protein covalently linked to the 5′ end of their RNA genome, principally picornaviruses, caliciviruses, astroviruses and potyviruses. With picornaviruses the VPg is very small and plays no role in the synthesis of viral proteins. In contrast the VPg proteins from the other families are larger (typically 13-15kDa) and are involved in ribosome recruitment and translation initiation.

We and others (particularly Michele Hardy’s lab) have shown that the VPg protein from caliciviruses, including human norovirus binds to cellular translation initiation factors and that this interaction is essential for viral protein synthesis. These viruses have effectively evolved a proteinaceous cap-substitute. Like IRES mediated translation, it appears the VPg proteins from different caliciviruses behave slightly differently and we are trying to figure out these differences as well as trying to figure out precisely what initiation factors are involved.

The data on astroviruses is not quite as developed, but work from Susana Guix in Barcelona has shown that the linkage of VPg to viral RNA is required for infectivity as removal of VPg from purified viral RNA using proteinase K significantly reduces the infectivity of the viral RNA. One would then predict that it is also involved in viral protein synthesis.

The potyvirus story is really cool as it appears that the ability of VPg to bind to initiation factors is a major determinant of whether one particular species of plant is susceptible or not to infection and may even be an example of how viruses could affect or drive the selection of resistant variants.

Keep up the fantastic work



Professor Ian Goodfellow

Head of the Division of Virology

Wellcome Senior Fellow

Department of Pathology

University of Cambridge



Dirk writes:

Nice detective story in the attached. There are now different papers showing that inhibition of purine or pyrimidine synthesis directly induces the expression of ISG’s (references within). This explains their broad-antiviral activity.

How might this have evolved? Does a cell use purine/pyrimidine concentrations as a virus sensor?

Thanks for the great podcast,



Dirk Jochmans, PhD

Research Manager

Rega Institute for Medical Research

University of Leuven (KU Leuven)


Adam writes:

Hi TWiV Team,

Thought this paper might make a good subject for a future episode.

As it turns out, some small percentage of the human population carry a latent copy of human herpes virus 6 in a telomeric region of their genome. Presence of the integrated virus genome induces breakdown of the telomeres, resulting in the occasional release of a complete, and potentially functional, HHV6 genome. Interestingly, the same degradation of telomeres is not seen in germline cells with the same integration.

Has this kind of intergenerational-latency been observed in other eukaryotes? The observation that germ cells are spared from an early death makes this seem more a strategy than an accident.

If this were a reproductive strategy of the virus, what advantages do you suppose it would gain that could not have been achieved by direct host to host transmission?

Phage would be the classic example for vertical transmission of a latent virus. Though I think the rules of the game are different in bacteria: phage are letting the host do the hard work of enumerating their genome, and will tend to ‘jump ship’ only when it begins to sink (UV, heat stress etc), in search of a fitter subset of the fleet.

HHV6, however, doesn’t wait until the host is dying to remerge. Likewise, the virus is not particularly fatal, so it’s probably not waiting for a latent host to move it to a new susceptible population. It would seem that HHV6 goes dormant for a time and occasionally reemerges to meet much the same host population as before. What is its game?

Do herpes viruses result in a sterilising immunity in the host population? If an immune host is just as good as a dead one to a virus, perhaps HHV6 is waiting for a generation of resistant individuals to be brushed aside.

Anyway, that’s enough from me.


Melbourne (Windy, 24C)

PS: Vincent, what is the conference you are speaking at in Melbourne next year? I’d like to make sure I’m there!

Luis writes:

Dear Twivers,

Thank you very much for your wonderful podcast. First, I should apologize because in my last e-mail I mentioned all of you, except Dickson Despommier. I am very sorry, particularly because I miss him when he is not in the show. As in previous occasions I would like to make another contribution to the picks of the week, particularly because today I had the opportunity to read a short article in the New York Times on the next pandemics by David Quammen, the author of “Spillover: Animal Infections and the Next Human Pandemic”:

This is a timely article for me, because it came out while I was reading the book. This is rather extensive but entertaining volume, and I would like to recommend it to all of you. It covers mostly viruses, and the classical recent virus outbreaks (e.g. Hendra, Ebola, SARS, HIV, etc), but it also deals with important bacterial outbreaks and I found it quite balanced in terms of scientific content and personal histories and adventures.

Hope that it wasn’t picked up before… (even considering the A. Gide’s statement).

All the best,


P.S.: Today, we have clear skies, with an actual temperature of 16ºC

(61ºF), at 11 a.m. (local time)


Luis Menéndez-Arias

Centro de Biología Molecular Severo Ochoa (CSIC-UAM)



Luc writes:

Hi TWiV team,

Lowly engineer here, stumbled onto your show and like most of your listeners fell in love with it and am trying to find time to catch up with the back episodes.

Your shows are so exciting that, like the story of one chap in your back episodes, I almost want to change subjects to Virology or even bioinformatics but for now your show gives me the escapism I need.

Your recent episode on your upcoming “Principles of Virology” was very interesting if not a nice pitch for the book – I too work on standards committees and could very much relate and laugh with your experiences, especially the group readings – I can tell you its a pain over internet phone!

I know you talked about making e-only version 4, and that 3 was paper only, but being desperate I scoured the internet to find that ASM Press does have their own ePub of revision 3., I thought that would be good for your listeners to know about as its really a wonderful book, and for those that can’t wait the months or year until the next revision this is fantastic way to reduce their carry-on weight / backpack weight when on the move.

Keep up the good work,

Lots of love,

An avid fan – Luc

ps. Weather in Korea / Japan is as hot as 41C (106 F), with humidity at around 50-55%.

Cassie writes:

Hello Professor!

Thank you in advance for taking the time to read this email. I just recently started listening to your podcast and I’m a fan of all the TWIs! I would like to pursue a graduate degree or certificate program in microbiology or a related field and I already have an undergraduate degree. Unfortunately dance is not an even remotely related field of study. I have thought long and hard about this career change and I realize that it will take some serious work to make it happen. My question is simply, what do I need to do to get people to take me seriously? I graduated from a conservatory program so I don’t have a whole lot of useful credits. Do I need to just start over with a new undergrad? Should I try getting the required credits before applying to grad programs or do you know of any schools that would accept me on probationary status? I know you get a lot of emails for advice thank you for reading yet another one, I’ve been spinning my wheels with my specific situation.

Thank you so much for your time and help!

PS it’s 34C/93F here in Austin, TX…even at 10pm

Randi writes:

Hey there!

I was wondering if any of you guys were going to the New England Conference of Science and Skepticism in the spring. I know it is early but this is the first year I am able to go and am super excited. I would love to meet you guys or even hear a live podcast!

I am a medical lab scientist at a large university hospital and share my twim/twip/twiv findings with anyone in the lab who will listen! Thank you for spreading the knowledge!


Eric writes:

Hello Vincent and Kathy -

I’m a big fan. I teach undergraduate virology at University of Alaska Anchorage, and we have a strong program in biology for undergraduate students (referring to the email from the student looking for an undergrad micro major).

for a PhD program – go to the lower 48 or look at UAA and UAF!

Best wishes and keep up the amazing work! I assign TWiV in my class!

Eric Bortz

Eric Bortz, PhD

Assistant Professor

Dept. of Biological Sciences

University of Alaska Anchorage

Johnye writes:


I’m certain she will have her seasonal flu as soon as she is old enough.

Johnye Ballenger, M. D., FAAP

West Cambridge Pediatric & Adolescent Medicine

Cambridge MA 02138-4627


Melissa writes:

This article is old but I thought it was funny and I’ve never heard this website mentioned on TWiV. Here is the link:

I LOVE all TWiP, TWiV and related shows. I encourage folks of all backgrounds to listen. My background is in Health Psychology, but I have always been fascinated by microbiology.

Thank you and keep it up!

Ken writes:

Hi TWIVers:

I plan to write more emails later, but I want to give you a TWIV Listener Pick of the Week – the movie “Gravity”.

After hearing a review by two real astronauts of the movie “Gravity”, I decided to take my son to see it (in 3-D) last weekend. My son is currently studying for his Bachelor’s in Aeronautical & Astronautical Engineering so I figured it would be great to get his opinion. After the movie I asked what he thought. He said first of all that there was no way that you could get from the orbit of the Hubble space telescope to the orbit of the International Space Station with a jet pack. But then he casually told me that the movie correctly placed every button and display in the Soyuz and Shenzhou capsules. I wasn’t quite sure if I should be more impressed that Hollywood correctly modeled the spacecraft, or that my son could tell by looking that they were correct, but I’ll go with being more impressed by my son. Then I asked if he still wanted to be an astronaut. I figured [SPOILER ALERT] that seeing the Hubble Telescope, the Space Shuttle, the International Space Station, a Soyuz capsule, and the Chinese Space Station all turned into charred orbital debris, he would pick another career. “Of course I still want to be an astronaut!” he replied enthusiastically. And I told him that when he applied for the astronaut corps, I would as well.

The movie had incredible special effects of course, and the physics of being in space is mostly correct. Apparently almost all of the spacecraft and space scenes were CGI (Computer Generated Imagery) and only the actors were filmed as they were suspended by wires in a giant light box. The scenery is spectacular, and definitely worth seeing – even by those of us who normally don’t go to movie theaters.

Keep up the great podcast!