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TWiV 151 Letters

Stephen writes:

Wildebeest (Gnu) are ruminants as they belong to the family bovidae like the domestic cow etc. Whereas Zebra belong to the family equidae and are monogastrics.

Again a great show.

Stephen

Judi writes:

Finally- I can help you guys

PBS has a great evolution series (and an associated website http://www.pbs.org/wgbh/evolution/

The videos are good... may need additional info to update.

and then there is the understanding evolution website from UC Berkeley school of paleontology

http://evolution.berkeley.edu/

So glad I get to give back!

Judi

(High school and community college college person)

PS yes - please to the virology 101 podcasts! and keep up the bad jokes and puns

Christos writes:

I have two comments about your latest episode:

1. You read a letter by a neurologist about virus reactivation during immune-modulator therapies and he asked you for examples. You mentioned herpes reactivation during natalizumab therapy. His comment is correct and I guess we will see many more of these cases in the coming years when more biologics immuno-modulators are used. Currently, the most common example of virus reactivation is Hepatitis B during all kinds of anti-TNF treatments (including several antibodies). There are several reports out there and in some countries there is active monitoring of HepB levels during treatment.

2. In a lighter note, you mentioned Bachmann's comments on the HPV vaccine. This is a video in the Colbert report making fun of the whole issue: http://www.colbertnation.com/the-colbert-report-videos/396674/september-14-2011/rick-perry-s-hpv-vaccine-mandate

Best,

Christos

David writes:

Virii guys,

In episode 139, in response to a letter from Eric, Vincent (at about the 1:00:00 mark) made reference to a paper detailing evidence of viruses contained in genomes extending back about 150 million years. Vincent stated he would put a link in the show notes, but I didn't find it there. Would you please put in that link? I would be interested in reading this paper.

[see http://www.virology.ws/2010/12/10/unexpected-endogenous-viruses/ ]

In episode 141, in part of the discussion about Alan's pick of the week, there are a few things that to add or correct. The Permian was from 300 to 251 million years ago, not 100 million years ago as Alan stated. Rich asked about what kinds of animals were around, and Alan mentioned Dimetrodons (the sail-back animal that looks like a dinosaur). A Dimetrodon fun fact: We (as a representative of mammals) are more closely related to Dimetrodons than dinosaurs. Dimetrodons are part of the class Synapsids, referred to as 'proto-mammals', from which mammals evolved. There were also Gorgons, which had big canines sort of like sabre-tooth cats. Some of the first marine reptiles existed then. All of the landmass was part of a single supercontinent name Pangaea. The Permian ended with the largest mass extinction event (the "mother of all mass extinctions"), when an estimated 90-95% of all marine species and 70% terrestrial species went extinct. By comparison, the last big mass extinction, the one that got the dinosaurs, only rated a puny 75% species extinction :)

-- David

Jim writes:

Hi Vince et al,

I heard a Ted talk by Angela Belcher on using nature to construct batteries, fuel cells, etc. Viruses are used to move genetic material to bacteria to make materials like abalone and diatomes make.

I vaguely recall a pick of the week for viruses being used in batteries??? If the Angela Belcher talk is different from this it may be of interest.

I am a devoted fan of TWIV, TWIP, and TWIM. It is a privilege to be able to hear you and your colleagues talk.

73,

Jim

Richard writes:

Dear Virologists,

May I try again on Heisenberg? One of the first things a student in physics learns is that we probably know less than 5% of everything there is to know about the universe. And further they learn that we probably never will know all there is to know or even a significant portion of what there is to know. (Indeed there is even one point of view that the human brain, at its current level of development, may not be capable of understanding certain things, but that is another topic.) This leads to a certain level of modesty on the part of physicists about their power to understand any topic. Did I detect a certain sense on your part that virologists are gradually learning all there is to know about viruses and eventually there will be no uncertainties? Yes, Heisenberg's use of uncertainty is different than the uncertainty of undiscovered phenomena but in the larger philosophical context the point is that no matter how much we study something, it is very, very likely that we will ever understand it in every detail. And I wonder if the more you study and understand viruses, you uncover more questions than you do answers. What do you think?

I forgot to mention that my training is in relativistic quantum mechanics but have become an amateur virologist.

By the way, the virology I work on is of dengue. Your TWIV 147 on dengue and Wolbachia was superb. What do you think are the chances that dengue will become a more virulent virus as it tries to evade Wolbachi in mosquitoes. Are there any precedents?

All the best,

Rich

Richard Mahoney, PhD

Coordinator, Policy & Access

Dengue Vaccine Initiative

International Vaccine Institute

Seoul, Korea

Derek writes:

Hello TWIV,

I love your podcasts. I'm a PhD student in Victoria, BC and drove to San Francisco and back this summer and spent the whole drive catching up on past TWIV episodes. I think I'm saturated!

In podcast 146, you had a pick of the week from the DIY Bio space which happens to be what I was in SF for. There is a new community lab called biocurious that some of your listeners may be interested in, it provides a space to explore wetlab biology in a more casual setting than pursuing an academic degree. http://biocurious.org

Also, Eri Gentry and I have just launched a podcast of our own that may interest your listeners. Garagebio is a podcast devoted to exploring what happens when you put the hottest new biology discoveries in the hands of amateurs and small-scale startups. http://garagebio.org

You're an inspiration - keep up the great podcasts!

Best regards,

--Derek

Lili writes:

To All Who Make TWiV Happen:

Thanks so much for all the great information on your netcast. I'm a non-scientist, newly introduced to your program, and I'm tuning in every week now. It's an absolute treat to listen to scientists talk in an absolutely fascinating manner about such a vast array of topics having to do with virology. TWiV 149, where you chat with Trine Tsouderos, was a real eye-opener for me, in particular, and I've taken the opportunity to read several of Trine's informative articles that you've linked to the program.

Cheers,

Lili

Peter writes:

Dear TWIVsters,

I am a UK listener and, having recently discovered your excellent podcast, have been doing my best to catch up.

I'm not quite up to date yet so apologies if you have already discussed this but I would be really interested to hear what you guys think about the potential for phage therapy to support or even eventually replace antibiotics. I found this topic fascinating and looked to pursue it both as an undergraduate in biology and a during my MPH. Almost as fascinating is that none of my professors ever seem excited by its potential!

It would be great to hear your views on the topic,

keep up the good work,

Peter

Arnold writes:

Dear Rich,

in one of the last TWiV-shows you said, that HIV is the only RNA virus, which integrates in the host genome. This is not true. You might have missed the papers about Bornavirus or Ebolavirus which showed, that these viruses can or at least did partly integrate in thel genome of its host.

So did you miss these papers or do you have a different opinion on that?

I did not want to say, that it was not an accident. And it is also not obligate for these viruses, I know. But it has happened and maintained - and still might happen. And it also seems not to have a disadvantage neither to the host nor to the virus. One can even turn this and think about if this might have had a beneficial effect for one or both, even though it is no obligate feature.

As always, when people start to dig in things, it turns out to be that there is not only black and white, but also grey - maybe this is the only thing I wanted to say ;-)

Best

Arnold

--

Department of Virology - University of Freiburg

Germany

Jason ‘XenoPhage’ writes:

in a previous TWiV, 126 to be precise, you talk about the HPV vaccine. Again, if I understand correctly, you mention that if someone is infected with HPV, they don't generate antibodies, but that injection of the HPV vaccine does cause generation of antibodies. I believe the question of why was asked, but there was no known answer. Is it possible that with a full-on infection, the virus is able to somehow evade the immune system, effectively preventing the creation of antibodies, but the vaccine is an attenuated form of HPV, allowing the immune system full access to the virus? Just some random speculation from a non-virologist.

Thanks

Jason

---------------------------

"Something mysterious is formed, born in the silent void. Waiting alone and unmoving, it is at once still and yet in constant motion. It is the source of all programs. I do not know its name, so I will call it the Tao of Programming."

Michelle Ozbun replies:

This is a good issue requiring clarification. Only a fraction of those with detectable HPV DNA will show an antibody titer, suggesting that a small dose might be able to infect but not generate a measurable immune response. Yes, we know that during infection the virus evades the host immune response quite well. Exposure to the virus does not normally result in inflammation (which is important for an immune response). The skin is an immunologically privileged site and the virus is not lytic and escapes via shedding of dead skin cells. Therefore, antibody titer is not a good measure of whether someone has been infected previously. Viral DNA or sometimes viral transcript detection is the measure of current infection.

Conversely, the HPV vaccine is a pretty high dose of a "subunit" type "virus-like particle" (VLP) preparation with adjuvant (alum) that is injected intramuscularly. The VLP cannot replicate but because of the high dose, route of inoculation, the adjuvant (which causes inflammation), and the fact that the major capsid protein L1 is present in repetitive capsomeric structures (360 copies of L1 arranged in 72 pentamers), the vaccine elicits a strong protective antibody response. The antibody response shows efficacy in protection to well over 5 years of follow-up.

Hope this helps to clear up the difference in exposure and immune response.

Levi writes:

Hi Vince,

It was great to see you at ASV. I just wanted to note that I'm currently watching Ian Lipkin on Charlie Rose. He's there speaking about the film Contagion, which is about a deadly viral pandemic. Like you, I'm often disappointed with the portrayal of science in film and television. I know exactly what you were talking about when you mentioned NCIS on your TWiV about zinc-finger nucleases. Because of this, I don't usually watch such shows or films because I know they'll get it wrong and I wont be able to suspend disbelief and enjoy the work.

However, since reading a couple of good reviews, and now seeing a respected scientist involved with the project, I'm tempted to see the film. I'd be interested to know if you or the rest of the TWiV team have seen it. If so, what are your impressions? I, for one, would love to a see a film that accurately depicts the work of those involved with infectious disease and public health. As virologists, we know many true stories that are more "thrilling" than any Hollywood script (hantavirus at Four Corners comes to mind).

But maybe, as virologists, we are biased. Maybe people who are so fascinated by reality find fiction a bit disappointing or unnecessary.

Thanks for all the great TWiVs so far, and keep up the great work!

--

Levi

Alex writes:

Hello Doctor Racaniello and fellow TWIVzors!

I apologize in advance with the wide spectrum of this email, been meaning to write for a while now.

I extremely enjoyed TWIP#29:Neglected Tropical Diseases with Peter Hotez. It was very inciteful to hear about the neglected tropical diseases and how mortality rate is not always the clearest way to measure the impact of a particular disease. I was wondering if you might be able to inquire him on why he selected the MD/Ph D program in his education. I've only recently become aware of this route offered by many medical schools and wondering if he might talk a little on the advantages and disadvantages. While seven years seems like a rather large commitment of time- it appears as though it blends both treatment and novel research well. Additionally, I am also curious in how it is best to approach a faculty member when looking for a mentor for a research project. Reading their current fields of research online is a good start, but I'm not exactly sure where to go from there. Most of the medical schools that I have been investigating require you to have a clear idea of what you intend to research and with who- at the time you apply.

Regarding TWIV#147, I was slightly saddened that the quintessential theoretical endosymbyote was not mentioned. You guessed it, the mighty mitochondria! I know several studies have suggested this organelle was once an independent bacteria that may have fused with a eukaryote cell at some point in it's lineage. Perhaps one of the oldest examples of mutualism- where the host eukaryote cell gains ATP energy while the bacteria gains protection from the outside environment. How would one explain the presence of unique RNA within the mitochondria otherwise?

Also, is there such a thing as an exosymbiote? Benign bacteria of the gut such falling in the genus of Bacteroides, Clostridium and Fusobacterium seem like they could be labeled as this. The host is protected from more virulent species while the bacteria gets a free source of nutrition.

Finally, I'm glad to see that the movie Contagion didn't fall under TWIV's radar, as it was selected as a weekly pick in TWIV#148. Thought I might help simulate some conversion on things that I picked up on during the course of the movie. The following contains spoilers so I suggest you view the movie before reading further...[saved for a future episode].

Thank you for all the diligent work on TWIV! Episode #150 will soon be here, quite a milestone to say the least.

Cheers,

Alex

Bachelor of Science

Charles writes:

Hello TWIVers

In a recent episode there was a passing mention of the fact that, for a cell, a defeated virus is also a source of nucleotides. I was wondering if there are any organisms that deliberately encourage virus penetration, confident that they can neutralise the viruses and then use them as a food supply. Or is this too dangerous a strategy to have evolved?

It seems to me (from my dubious position as a Software Engineer whose knowledge of biology is largely due to your podcasts and Wikipedia searches) that a possible candidate might be a bacteria living inside another organism, luring in viruses that infect its host. As the viruses would have evolved to infect the host rather than the bacteria, inviting them inside might not be immediately suicidal.

Thank you all very much for the work you put into making TWIV. I never miss an episode. May you long continue.

Kindest regards,

Charles

York, UK

Jeffrey writes:

Dear Dr. Racaniello - recently you edited a PLOS Pathogens paper "The Fecal Viral Flora of Wild Rodents" (http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002218) and I had a question that doesn't need an immediate answer, but perhaps could be addressed in a future TWIV. The authors isolated these viruses through filtration, treating the filtrate with DNAse and RNAse to nix any unprotected nucleic acids. I found it interesting that ~40% of their reads were bacterial and ~2% were eukaryotic. Are these what you would expect from schmootz sticking to the filter? Do you think its possible that these represent phage that are caught mid-transduction (in the case of the bacterial sequences) and maybe eukaryotic viruses doing the same? Just dreaming like a 2nd year graduate student.

That is the question, now the plea: are there any plans to do a program on the various papers that have come out on viruses in the feces of different animals. Ever since graduate school working on adenovirus at Emory Univ, I had wanted to look in day care poopy diapers to address questions of adenovrius excretion and sequence evolution. Now I am a full time teacher at a community college near Atlanta, but I find myself working with others in my department trying to get a shoestring program together to have our non-majors students collecting coyote poop so that we can extract DNA for sequencing to have students look at real world, local applications of what they are learning in class. So far all I have is several coyote scats stored in the freezer and am looking at what exactly we should be amplifying for sequencing. It's a tougher problem than I had initially thought it would be. Forgive me if you have already done a program like this (I will get to it), but you guys really serve as a weekly (sometimes bi-weekly) lab meeting/journal club for me and help keep me not only current, but excited to bring "hot off the press" science to my students who would otherwise not likely think about these things.

The pepper mottle virus-in-human-feces story would be a GREAT way to get Senor Despommier into the studio as it brings up issues that he specializes on (relationships between different species and the poop-agriculture-pathogen/parasite triad). I would love to hear his opinion of whether he would consider humans to be a vector for this virus.

I consider the communication of science and how it works to my non-science major students to be one of the most important things I do and you really inspire me. We may try to do a simpler version of what you do, but with the focus on the amazing diversity of plants and insects we have around our rural campus.

Thank you for a very entertaining and patently useful program.

Jeff

Eric Delwart replies:

Great question which I'll rephrase as why don't we get 100% viral sequences since we "purify" for capsid protected nucleic acids ? A lots of the bacterial and eukaryotic hits are to ribosomal sequences which we reckon are partly protected from nuclease digestion due to their being in a tight complex with proteins. Ribosomes are also about the diameter of a small virus and can easily go through our 400nm filters. Our definition of viral is also quite stringent at E score< 0.00001 so we might actualy have more (divergent) viruses than we report. A lots of the sequences had hits to phages so the proportion of viral sequences (both prokaryotic and eukaryotic) is actually ~13%. I reckon a lot of that background is due to bacterial/protozoa/host DNA and RNA being in some form of small Schmutzy complex with proteins/lipids/glycos and surviving the nuclease treatment. We did notice that these rodents had a very low ratio of eukaryotic virus hits to total sequences relative we saw with other mammals like bats, sea lions, pigs. I think this reflects a generally lower enteric viral load. This may be due to a relatively more isolated life styles for rodents and possibly older age of the feces donors (a lot of the sea lions and pigs were < 1YO).

Peter writes:

as a long time listener of twiv, twip and twim, you and Vincent almost seem like old friends to me, thus it feels somehow special to find your name and your vertical farm project mentioned in the large German periodical "der SPIEGEL".

Let me take this opportunity to thank you for the work you're doing. The way you're shedding light on microscopic life and not-so-life is the best educational entertainment and the most entertaining education I know. My amazement about the interwovenness of all life has grown beyond my wildest beliefs and I'm sure I've only just scratched the surface.

http://m.spiegel.de/wissenschaft/mensch/a-773724.html#spRedirectedFrom=www

Jason writes:

Hello TWiV. I am a physicist pretending lately to be a biologist (BS in Math and Physics and now attempting a MS in biology). I was looking for new podcasts recently to listen to for a road trip and came across TWiV starting at around #132. I must say it was a very educational road trip indeed and have been enjoying trying to catch up from TWiV#1. It's been a few months now, but I remember a conversation about HPV and some of the talkers were from UF down here in sunny Florida. Just wanted to see if they caught the HPV article UNF's student newspaper published around that same time. Caught some very interesting publicity off their choice of cover picture for the article. I thought it was interesting grab to educate the students at UNF that HPV might not be only a female type problem and the dangers in oral sex, and found it funny that I heard a comment on TWiV just after that about throat cancer risks with HPV. Take care and hopefully sometime this year I'll catch up before taking my first virology class. My project will have something to do with oral inoculation of arbovirus in mosquitoes and find the little pests very interesting, both of them!

-Jason

UNF

Here is a link to the cover photo for the UNF paper

http://www.outsidethebeltway.com/unf-oral-sex-photo-controversy/

Steve writes:

Hi Alan and Rich,

Superb job co-hosting TWIV #145. You didn't miss a beat.

Just a small bookkeeping note. The hyperlink to the listener pick of the week is currently incorrectly to the "Small Pox and its eradication" pdf article and not to the "Science Photo Library" webpage. Thanks for fixing this hyperlink.

Keep up the great work, I so enjoy your show and look forward to the Sunday download which I listen to on Sunday evening.

Warm regards,

Steve, MD

Dave writes:

Dear TWiVers,

It was great to have seen the live podcast at ASV! I am looking forward to seeing another one next year in Madison…

I was curious to hear what kind of reactions you had to the July 27 PLoS One paper (Rider TH, Zook CE, Boettcher TL, Wick ST, Pancoast JS, et al. (2011) Broad-Spectrum Antiviral Therapeutics. PLoS ONE 6(7): e22572. doi:10.1371/journal.pone.0022572). The news headlines that I saw were akin to "drug that could cure any viral infection." While trying (specifically) to target cells possessing viral double stranded RNAs seems like a reasonable approach, do you think this DRACO approach actually has the potential to be a broad-spectrum antiviral (ignoring, for now, any possible issues with drug delivery…)?

Thanks in advance for any thoughts…

Keep up the great work…

Cheers,

Dave

P.S. I wanted to share that this Spring, I had my undergraduate virology students use TWiV to learn about potential pieces of literature that they could then download and read as the basis for their in-class oral presentations. Overall, the students liked hearing a little context about the paper from TWiV before going through it themselves in detail to prep for their talks about the experiments/data. An added bonus of the exercise was that a number of them now are regular TWiV listeners!

---------------------------------------

David B. Kushner, Ph.D.

Associate Professor of Biology

Dickinson College

Robin M.D. writes:

Vincent and Dickson

Listen, I love you guys and don't want to get anyone in trouble, but someone should address our government's preoccupation this last decade with the development of offensive bioweapons.

Because both of you are retired and no longer dependent on government grants you can speak freely, where most others cannot.

Please find included a excerpt of a recent essay on the subject:

By H. Patricia Hynes

Excerpted from: truth-out.org

“. . . From 1942 until the late '60s, a highly secretive, offensive, biological weapons research program, [originated] at the US Army's research facility at Fort Detrick in Frederick, Maryland, gained momentum. World War II German and Japanese scientists, whose war crimes were overlooked were employed there. . .

In 2001, the US Department of Homeland Security began aggressively promoting ‘research’ on biological warfare. The new agency used the anthrax attack that same year, in which anthrax was sent through the US mail to liberal Congressional politicians and journalists, to gain public support for biological weapon ‘research’.

Some have suggested that the domestic terrorism was a deliberate act perpetrated by Homeland Security. Regardless, as a result, the act of terrorism set off a massive flow of federal funding for research on live, virulent bioweapons. . .

Today, in dozens of newly sprung laboratories, research on the most lethal bacteria and viruses with no known cure is being conducted in an atmosphere of secrecy, with hand-picked internal review boards, with no public oversight or accountability. . .

Fort Detrick, Maryland, a military base and major government research facility, is the site of the largest biodefense lab. Here, biowarfare pathogens are created, including new genetically engineered viruses and bacteria. Novel methods of delivery in biowarfare are also being tested. . .

[Despite denials by this and the previous administration], Fort Detrick's research agenda - - modifying and dispersing lethal and genetically modified organisms - - is clearly and unmistakably an offensive weapons program. . .

By 2009, 400 facilities and 15,000 people were handling biological weapons in sites throughout the country, in many cases unbeknownst to the local community. The $60 billion spent since 2002 on biological weapons research has raised serious concerns for concerned scientists and for informed critics. . .

A Washington Post story revealed that an inventory of deadly pathogens at the government's premier bioweapons research laboratory at Fort Detrick, Maryland, uncovered that more than 9,000 vials were missing.

In testimony to a House Committee hearing on the proliferation of bioweapons laboratories, Nancy Kingsbury of the GAO revealed that expansion of bioweapons laboratories has been ‘so uncoordinated that no federal agency knows how many exist’; nor is there any sense among federal agencies of their operational safety or the risks they pose to the public.

Keith Rhodes, the GAO's chief technologist, testified in the same 2007 Congressional hearing: ‘We are at greater risk today' of an infectious disease epidemic because of the great increase in biolaboratories and the absence of oversight they receive.’ . . .”

Joerg writes:

Hi Twivers,

I’d like to make a correction/comment to a statement made on TWiV 146 at 59:30 - 1:00:00 (not sure how to properly cite podcasts?):

“No one has ever purified MHC molecules and has done sequence analysis to see which sequences of HIV epitopes are in MHC molecules.”

Whilst it appears that no one has eluted peptides from HIV-infected cells – epitopes were eluted from MHC class I molecules from cells infected with HIV-recombinant vaccinia virus– see abstract below and cells transfected with HIV DNA (see attached paper by Tsomides et al.)

This field of research combined with work on synthetic peptides have confirmed the nature of the epitopes and the T cells that recognise them.

The use of transfectants and vaccinia recombinants rather than HIV-infected CD4 T cells may have had practical reasons since large quantities of infected cells are or at least were required to elute and indentify the peptide epitopes.

As somebody who spend a good part of his PhD growing large quantities of melanoma cells in order to elute and identify peptide epitopes recognised by cytotoxic T cells I kind of felt strongly about this point.

Anyway suffice to say that I really enjoy your podcasts as I continuously learn a lot.

Keep up the great work you’re doing.

Regards

Joerg, Munich, Germany

Eur J Immunol. 2000 Sep;30(9):2521-30.

A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules.

Tomiyama H, Yamada N, Komatsu H, Hirayama K, Takiguchi M.

Also J Ex Med vol 180: 1283, 1994

 

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