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Are you, Alan Dove and Prof. Racaniello, saying you think Mikovits and/or others on the Lombardi paper lied about the results or blinding? I think circumspection is a natural human reaction to the allegations of theft that have been made against Dr. Mikovits (my impression is that she was at least out of line, maybe worse, but I think we need to wait for all the evidence in those cases to come out before we make final conclusions).
And this rigorous study by Lipkin won't be believed by you, you say, if the results confirm the Lombardi paper- the burden is on them, not the other less rigorous studies.
You guys do make some good points. There are multiple lines of evidence against XMRV infecting humans in vivo. However, your assumptions and conclusions about the "pro-HGRV" scientists seem to me to be biased once again as compare to your conclusions about the "anti-HGRV" scientists and your silence on the outright fraudulent 'scientists' involved in XMRV and in ME science in general- eg CDC, Wessely school including McClure.
There is some circumstantial evidence of potential 'sketchiness' re Mikovits and you have no problem assuming the worst (which is a normal human reaction), but why the double standard when it comes to the "other side" - the proven frauds who wage war on ME science? I have asked this numerous times and don't get an answer.
I appreciate that you published David Tuller's piece on CDC, but that's all you've done. In this podcast you mentioned that he wrote the piece but you didn't mention that it's another documentation of the fake science done on ME by CDC. I can't think of another way to explain it but bias.
I believe the main problem some conservatives have with gardasil (sp?) is that the abstinence only sex education programs in a lot of areas focus on "sex will kill you" type messages. HPV is one of the pillars of their argument. You can't say "Don't have sex at all or you're likely to catch this very prevalent virus that can cause cancer." if your students have been vaccinated against the main cancer causing strains.
Great men of TWIV,
I’m a new virology/immunology postdoc, and I am very glad your podcast exists to remind me of all the virus out there I don’t personally work on. Before I started listening I had forgotten all the details of everything except herpesviruses and poxviruses. You have a great camaraderie — no matter how interesting the subject matter, I wouldn’t be able to listen if you sounded boring. For some reason I was surprised to see that Rich Condit does not have a beard.
I’d like to know what you think of this paper: http://dx.doi.org/10.1016/j.chom.2011.07.010 (Manley et al , Human Cytomegalovirus Escapes a Naturally Occurring Neutralizing Antibody by Incorporating It into Assembling Virions. Cell Host and Microbe 10:197)
One of the senior authors, Teresa Compton, gave a talk in our department recently and she made reference to some interesting finding that she wasn’t allowed to talk about. This seems like it is probably that finding.
The idea of a virus incorporating an antibody into infectious particles is weird. Although the authors say it “illustrates a general mechanism of viral antibody escape”, they don’t mention this happening with any other antibodies, against CMV glycoprotein H or any other CMV protein. Do you think this is a freak occurrence? Since antibody clones are unique to each person, I’d be surprised if a virus can evolve resistance against a single antibody clone. Especially a herpesvirus which does not exactly have a high mutation rate.
Penn State M.S. Hershey College of Medicine
For viruses like CMV(cytomegalovirus), HBV or HIV, those which is characterized of latent infection, what factor controls its re-activation, what priority its genome-encode proteins are expressed and what the virus can be detected as early as you can.
Take CMV for example, most people are naturally infected with it. However, for immunocompromised people, etc, CMV can re-activate from latent state and cause great impair to host. As those people is defiecient in immune system, thus their [health relies on a drug ...] healty completely lie in the exterior drug combating the CMV when it reactivates. In such cases, detection of CMV as early as we can is the critical issue in ensuring the life safety of the people.
Sincerely looking forward to your reply and any advice.
Laboratory of Structural Biology
Saul Silverstein writes:
No one knows what controls the switch from latency to virulence. More likely than not it is a manifestation of the host and site of infection. Changes in expression of host genes or activation of heatshock proteins may be the most likely explanation for release from latency.
I thought of a cool idea. I think it was Scientific American that used to do a historical look back at what was going on in science 50, 100 and 150 years ago. I reckon it would be great to pick a random virology/viral diseases article each week or month from 50 and 100 years ago and give a quick 30 second outline on what was going on, just to give us a bit of perspective on how far we have come.
Keep up the good work guys, you keep me company on the long drives to and from the lab each day. Actually I have all three podcasts TWIV, TWIP and TWIM on repeat in my car so I must have listened to each episode half a dozen times each. I am usually paying most of my attention to the traffic so I only absorb about 10% of what you are saying, which means I must be just over half way to hearing everything in the podcasts by now??
Anyway G'day from down under, the temperature is about 27DegC (? 81deg Fahrenheit ?) 25% humidity and a light breeze. Definitely a day for the beach :)
P.S I found the attached article yesterday I thought you might find it interesting.
You need a whale of a supercomputer to run a simulation like that, makes my little poliovirus virion simulations seem like minnows.
Senior Medical Scientist
National Enterovirus Reference Laboratory
WHO Poliomyelitis Regional Reference Laboratory
Victorian Infectious Diseases Reference Laboratory
He sent http://www.twiv.tv./11yt2114.pdf
Dear Vincent, Rich, Alan and Dickson
As a fairly recent listener to TWiV I have just been trying to catch up with the many past episodes.
In TWiV #5 Vince and guest Saul Silverstein discussed Herpes viruses.
I am in my early 50's and had chicken pox before I was ten, would it in your opinion be worth me seeking vaccination against varicella zoster to reduce my chances of suffering from shingles in the future?
You also spoke about postherpetic neuralgia as a symptom of zoster.
This brought to mind another podcast I listen to - Dr Ginger Cambel's Brain Science Podcast.
In BSP Episode 69 Ginger was talking to R. Douglas Fields about his book The Other Brain about the influence of the glial cells on the activity of neurons, including their link to chronic pain.
Is it known if as well as infecting neurons the virus infects the Schwann cells and causes them to release neurotransmitters that make the neurones hypersensitive?
I have heard that vitamin D can have an anti-inflammatory effect and that many people are deficient in vitamin D, would this mean that postherpetic neuralgia could possibly be relieved by either vitamin D supplements or creams or by photo-therapy with UV light to induce vitamin D synthesis directly in the skin?
If chronic neuralgia is due to glial sensitization what other treatments may be of benefit?
Sorry for my rambling questions.
[I am a photographer from the UK now living in Turkey]
Saul Silverstein writes:
There is no question that the vaccine is efficacious for those over 55 who wish to be protected from zoster, it's not 100% but it clearly works.
VZV is found predominantly in neurons but there is evidence that it also may be in the supporting satellite cells as well.
I have heard many times the Myxoma virus and the rabbits in Australia cited as an example of a parasite evolving and causing less harm to its host, and got very intrigued with the question of who was adapted to what. Specially after TWiM 19, when I heard that the Y. pestis from 14th century has been sequenced and harbors very few genetic differences in relation to the strains that circulate today, so that the pathogenicity of the bubonic plague should be in the 14th century Europeans health, not in the bacteria.
As I understand, Myxoma viruses from South American rabbits were introduced in Australia to kill the plague of European rabbits, that never had had contact with this virus. At first, the virus killed something like 99% of the rabbits, but in the latter years it caused less and less deaths, and nowadays it does not kill more. And this is always cited as an example of a parasite that evolved to preserve the host. But who has changed? Is it a change in virus pathogenicity, host resistance, or both?
This made me think if someone has done the following experiments: if the virus was selected to be less pathogenic, the recent Myxoma virus from Australia should not kill the rabbits in Europe. If the rabbit has been selected to be more resistant, as may have been the case of pest survivors in past, Australian rabbits grown with no contact with Myxoma vírus, with no previous immunity, should be resistant to the American original viral lineage. Do you know if someone has tested this?
Thank you again for the great podcast,
Grant McFadden answers:
Your TWIV listener asks a really great question that gets to the very heart of how virus-host co-evolution actually works out there in biology-land. Remember, the experiment of releasing pathogenic myxoma virus into feral populations of European rabbits in Australia has been cooking for only about 60 years now, which is pretty long from our perspective but only a blink of the eye in evolutionary terms. But at least we can say that, so far, selective genetic adaptations are occurring in both the viruses currently replicating in the wild, as well as the host rabbits that are now hopping about in the Australian outback. The original myxoma virus strain released into Australia around 1950, which originated from Brazil and is called SLS (Standard Laboratory Strain), has now evolved into a collection of virus isolates that cause reduced mortality in the current wild Australian rabbits, down from an original mortality rate of over 99% to current levels of anywhere from 10-60% mortality. Note that the virus continues to transmit efficiently between rabbits via biting insects, especially mosquitoes, and so has established an endemic relationship (called enzootic) with these wild rabbits. These populations continue to co-evolve and so we only can report on a snap shot of what we see so far.
We know that both the rabbits and viruses have changed genetically by mutual evolutionary pressures. If you take the current field rabbits that have not yet been exposed to myxoma virus and challenge them in the lab with the original SLS strain of virus, they are indeed more resistant to the killing effects and thus tend to live longer with less overall mortality. But, interestingly, if you take current virus isolates from the field and put them into the original fully-sensitive European rabbit strains, the death rate varies from much reduced from the original 99% to even more virulent (ie that kills rabbits even faster than the original SLS strain!). What this shows is that evolutionary co-selection pressure has generated not only more resistant rabbits but also a family of virus lineages with very varied virulence characteristics, and these are all competing with each other right now in the wild. We actually don't know which virus-rabbit pairings will “win out” in the long run, but at least we can say that the disease severity we now see in the Australian wild is uniformly dropping from an original near-universal mortality to one that is now much less lethal but still allows for efficient virus dissemination from rabbit-to-rabbit.
Unfortunately, we don't really understand what the genetic changes in either the virus or the rabbits are really doing at the molecular level. Attempts have begun to fully sequence representative wild virus isolate strains to compare them to the original SLS strain. Lots of sequence variations in these viruses will be documented, but establishing which ones are functional for disease and which ones are “silent” will take quite some time. On the rabbit side, we know even less: although the full sequence of the original European rabbit (Orytolagus cuniculis) has been reported, nobody I know is currently sequencing the feral virus-resistant rabbits that are now living in the Australian outback. With DNA sequencing costs dropping so dramatically, perhaps somebody out there will one day pursue this scientific question in detail. Maybe even one of your TWIV listeners?
Anyway, I hope these points help clarify the question.
Hello TWiV crew!
Quick question for Dr. Racaniello et al:
In TWiM_21, you mention (roughly around 30 minutes in) that viruses that have a long infection time have an incentive to inhibit apoptosis, which you had brought up because of its connection to lesser known mitochondrial functions (Ca2+ regulation, etc as opposed to only respiration).
In a recent lecture I attended, a review titled "Hallmarks of Cancer" (see attached) mentioned evasion of apoptosis to be one vital pathway in the sustained development of cancer cells into metastatic forms.
Is there any way to trace the development of oncogene associated viruses to inhibition of apoptosis, or do these two mechanisms function independently?
I haven't been able to study the full details of cancer-correlated viral infections, but I'd imagine tracing phylogenetic heritage is generally much more difficult in viruses, due to smaller genome size and huge mutation rates (compared to the host genome). [Does horizontal gene transfer occur among viral quasi-species?]
**Q2: lately, I've been trying to find an effective algorithm to determine the usefulness of various life sciences textbooks online, or at least a quick way to sort out hand-waving quacks and legitimate ground breakers. The problem with this is that the review process is often based on a pitifully small sample size (n is often less than 10), and contain concerns over a) the truthfulness/thoroughness of the review and b) the ability of the reviewer to accurately evaluate what the book has to offer. Given that the avg. cost of a textbook at or above the undergraduate level is nothing to shrug off, it's a bit of a problem.
One such book is "Evolutionary Dynamics" by Martin A. Nowak. From what I can discern, the book contains a treatment of theoretical biology from a highly mathematical (by a standard biology perspective) approach, but in being a relatively newer and interdisciplinary set of topics it presumably has the advantage of being both ignored by spare-time-deprived academics and potentially very useful.
While I realize a vast portion of his thesis may be invalid once the mathematical obfuscation is removed (default treatment of unknown author is skepticism; his work could easily be legitimate), I write to you about this primarily due to a supposed prediction made about the field of HIV research by Nowak.
If Google Scholar and citation number are worth anything, I believe the relevant publications can be found here.
If you could shed some light on this topic, it would be greatly appreciated. Thank you for your time.
As usual, the shows are fantastic! Keep up the excellent work.
he sent http://www.twiv.tv/hanahan.pdf
Dr. Raceniello & Esteemed Cohorts:
I am hoping that you would take the time to watch this video of Dr. Eric Schadt. You may know the basics -- and may want to fast forward through the beginning. This is the current location of the video:
Please comment on a couple items within the video. The items I like to hear your comments and discussion about:
· this extraordinary "gadget" he uses to analyze "real-time" and what it is doing and what he is doing at the molecular level and then at these systems level via computer modeling/simulation.
· And near the end of the video there is a very interesting virology/microbiology slide that he shows that he says is based upon unpublished data -- that he should publish pretty soon… so you may want to comment on this after it is published….
thank you for all the time that you all put into this podcast -- science education is so important!!
I just finished TWiV 160 with Dr. Moore. Great interview. I knew Dr. Moore and his wife Dr. Chang while I was doing my MS at the University of Pittsburgh. Great people, but I am really disappointed I never knew that Dr. Moore had an EIS background. I have had an interest in the EIS for many years now and hope to apply soon (when I finish my PhD, but who really knows how and when that happens). I know you have touched on the EIS program a few times, but it would be great if you could bring on some of the virologists that really made it famous e.g. Joseph McCormick, MD, CJ Peters, MD, or Peter Jahrling PhD.
A couple of messages to relay.
First to Dr. Despommier, the vertical farm project is alive and well in Chicago. I am sure he would be proud.
Second to Dr. Condit, tell him goodluck with his Personal Genome Project spit collection. I sent mine in about a month ago. Very interesting.
Thanks again for the great work all of you are doing,
Have you seen this picture of a T4 phage tattoo:
In 2007, science writer Carl Zimmer, having seen someone with a DNA tattoo wondered how common science inspired tattoos were. He asked readers of his blog and their response was massive.
Getting back to the are viruses alive question, I was having this discussion the other day and someone came up with one of the best answers I have heard to the question: "it's a bit like asking whether an photon is a wave or a particle"
Hi TWiV gang!
Love love love the podcast. I am a graduate student at the University of Washington and I have found your podcast both fun and informative as a student of virology.
I was wondering about a technique that was mentioned in episode 158 at the University of Michigan. Rich mentioned "mouse blots" when speaking with Kathy Spindler. I tried looking up this technique on pubmed and found a technique used by Louis Villarreal called "fluorography of whole mouse". I can't seem to find the publication in which Dr. Spindler describes this technique. Could you or Rich help me find it?
Thanks so much for this awesome service for the public!
Kathy Spindler replies:
The paper in which we used whole mouse blots is Ball et al. (1991) Virology 180:257-265 (PMID 1845825). We used 32P probes, which don't give as high resolution as some other isotopes (e.g., 3H used by Villarreal in the paper that Alison cites, but which uses a different approach - in situ autoradiography and whole mouse fluorography). I think some "modern" isotopes (33P- or 35S-labeled probes) might give better resolution than 32P with whole mouse blots? We haven't used the technique since the early 90s...
And I think you are right that Luis did invent the technology - the earliest paper I can find is Dubensky et al. 1984, JVI PMC255737 = PMID 6328007. Fig. 1 shows why we call it "slice mice."
Ian Lipkin, LPV, and Mike Oldstone are co-authors on a methods paper that I would have to walk to the library to get (horrors! it's 5 minutes away, inside the building!), but I've ordered it as a pdf online from the library and that should come in a day or so. I wonder if it will have a historic perspective on the technique. PMID 2670459 is that paper (1989). I can send that to you and/or Alison once it comes. I can also send her my "bench protocol" if she wants.
Those papers might have more detail than ours, where we merely cite Dubensky et al. and Rochford et al. (PNAS 1987, PMC304225). However, I note that we did mention that we had the microtome sitting in a Sears chest freezer!!! Kind of a useless detail...
First, I would like to say, I love the show, you guys make repetitive (but still awesome) lab work go much faster!
Before I get to my silliness, I'd like to ask a serious question or two, if I buy the microbe world app you guys get a good cut of the profits right?
Also, were any clustering analysis done on the H1N1 strain that were sequenced, if so did it prove that the strain jumped from swine to humans in mexico? (Sorry if the answer is common knowledge I'm only up to 2009 in your podcasts besides the few recent one's I've listened to).
Anyway, I'm not sure if you guys are aware of Reddit, but they just discovered that the sputnik virus can infect mammavirus. so in a redditors fashion I made this meme and thought I'd share! (here's the reddit thread http://www.reddit.com/r/todayilearned/comments/n13kg/til_that_some_viruses_are_so_large_other_viruses/)
my virology-related meme: http://www.quickmeme.com/meme/35f6dm/
I hope I didn't waste too much of your time on this silliness!
Hi Vincent, Dick and other hosts
I have a question that may be a little outside twivs remit, but at least partially applies.
Recently I have heard in podcasts (via stitcher radio), about the possibility of genetic engineering, of humans, and resurrecting the wooly mammoth. Some of the methods mentioned include cloning, and things outside of virology. However I was wondering if viruses, particularly retrovirus, would allow genes to be edited, removed, or inserted? If so would this be practical, or do better methods exist? Would it even be possible to engineer a retrovirus, so as to insert a gene, or other DNA, reliably into a host? Would this be a temporary change, or inherited by any offspring? My guess is that inserted genes would be inherited, as long as they where present in 'germ cells'. Much as the remains of retrovirus infections remain in many genomes. Also could a retrovirus be used to edit the genome of an elephant embryo, so as to make it match, say a wooly mammoth? My guess is that retroviruses aren't that big, and tend to insert things somewhat randomly. I'm thinking that would be a showstopper?
Some random speculation.... I wonder if it would be possible to engineer something, like a ribosome, that would edit DNA, given a template (either RNA, or DNA). So it would run along DNA, and compare the sequence to the template, on finding a match, it could then edit the bases, to match the rest of the template.
Thanks for the podcast, I listen to every episode, and like the way you simplify things enough for the non virologist, such as myself (I'm a water and waste water engineer).
Looking forward to more virology
Hi Vincent, dick and cohosts
I've just listened to the science show podcast from he 3rd December. They mention exosomes, a membrained container that is secreted by cells. These contain genetic material (RNA) as well as a number of proteins. I had no idea that the human body contained such a horizontal transport mechanism.
I can't help but compare these to a virus. Though there are clearly differences, do you think they are related? Maybe cells learned this trick from viruses, or the other way round?
Again thanks for your podcasts.
Dear Vincent (and Dick, Alan and Rich),
while waiting for the launching of a variant/sequel of TWiV to be broadcasted in spanish, as proposed by Estanis Nistal with the enthusiastic support of several other spanish-speaking listeners of TWiV, I have submitted a short notice for the journal "Virología", the bulletin of the Spanish Society for Virology (SEV, Sociedad Española de Virología) to divulgate your netcast.
The note was published in the volume 14, number 3, page 13. A free copy of the journal can be downloaded from:
The note intends to inform the virology community in Spain of the existence of TWiV, including links to Virology Blog and TWiV webpages.
I hope this information will contribute to spread the word about TWiV among spanish virologists, students and the general public.
With warm regards,
I am sure others will send you these links
About a series of Norovirus infections on an Air New Zealand plane, there was inadequate cleaning and disinfection between flights.
I have several times come down with fairly severe chest infections (one requiring hospital treatment) after flights it is of course difficult to know exactly where I acquired the infection but at the airport or on the aircraft seem most likely places to be exposed.
I am a regular listener to TWiV, TWiP and TWiM keep up the good work these are all fascinating and informative shows.
Dear TWiV team,
Happy holiday and happy new year.
Thanks a lot for the great virology blog.
I would like to know if there is any possibility to any virus to be fused with another one, to be infected by other virus?
As we know the infection concept is just a conscious term or scientific term to us, since it causes us to be sick [unwanted health condition] due to our reaction with micro-organisms such as viruses. If viruses are independent [not related to us] organisms, how would they get their compatible receptors to ours on our cells?
In Naica mine, a mine is best known for its extraordinary selenite crystals in the Mexican state of Chihuahua, virologists have discovered millions of viruses in many samples from underground water and crystals. The temperature in such a mine is nearly 50 degrees and the humidity is nearly 100%, after sucking out the emerging water in the cave, roughly for million years ago.
Maybe such these conditions are suitable to form the basic molecules for any living cells such as amino acids which are the basic building blocks of viruses. What if more than aboriginal or primitive viruses or separated molecules fused to form a single genetic material to generate new generation(s) or advanced virus(s)? Consequently, forming more advanced cells to form the aboriginal creatures such as bacteria, abiogenesis ?
All my family members work in a hospitals. There many excellent MD podcasts already. The thing I like about TWIM, TWIV and TWIP is precisely that they are different from those. Having a panelist who is a doc working in emerging diseases is interesting. Local doc stuff, not what i listen for. I listen to every episode of all 3 shows btw. Thanks for what you do.
I've been listening to TWIV podcasts at lunch for over a year. My anthropology degree from 40 years ago did not prepare me for TWIV, nor did my 30+ year computer software career. However, I've been reading Scientific American since the early '60s, and I subscribe to Science News, so I'm not completely lost.
All that being said, I heartily commend you for your excellent presentation of this subject matter in a way that helps us lay folk follow the story, while stimulating enthusiastic participation by your visiting specialists. Bravo!
Oddly enough, my grounding in anthropology is what prompts this comment. I hear lots of interviews on all kinds of subjects on radio, TV and podcasts. I can tell when a researcher is being interviewed, because almost every time they begin to answer a question they start with the word, "So." Sometimes it's part of an opening phrase, but more often it appears to be a sentence all by itsef.
And you TWIVians tend to follow the pattern when beginning your follow-up questions. (Replay a segment of one of your podcasts and count how many times you hear "paragraphs" start with "So."
Since anthropologists are not forbidden to ask the Why questions, I have a hypothesis as to why this happens.
A researcher's frame of mind is one of gathering evidence for chains of causality. "This and these get together, SO this happens." This pattern of thought may be carrying over into their patterns of speech. "Researchers think a certain way SO they speak a certain way."
So, ;-) keep up the good work, and try not to be too self-conscious about starting your comments with "So."
I found TWIV from a link on an ME/CFS web site when I was researching my wife's illness.
The variability of the symptoms, not just between patients but from day to day for one patient, has inspired my wife to refer to her illness as WBD (Wierd-Butt Disease). She can never predict how she will feel in a day or even in an hour. Occasionally when asked by acquaintances what illness she has, she says she's come down with WTF.
Recently Vincent theorized that the illness may have some kind of environmental trigger that, in vulnerable individuals, initiates a cascade of changes over a period of time that finally presents as something we characterize as CFIDS or ME/CFS or any of the other "spectrum" illnesses. At that point, there's no hope of identifying the long-gone trigger.
Although I find this theory very disheartening, my wife's medical history would not rule it out. She dates the major onset of her illness to the spring of 2005, but looking back she sees that many of her symptoms began to appear up to fifteen years earlier.
Vincent, I fear that you may be right.
Hi Vince et al
Heard a Ted talk which I enjoyed a lot. It gives a new way of looking at information to see if life might be present.
This has shifted my vote to thinking viruses are alive.
73 ( Best Wishes)
PS> here is my pick of the week (patient zero):
pretty darn good storytelling……
over the past few Twiv episodes, there has been increasing talk about what happens on a day-to-day basis in the life of a scientist (grad student, post-doc, PI, etc) and what life in the lab is like. A book I would recommend to those curious about this is Natural Obsessions by Natalie Angier. I was given this book by my boss when I was working as a technician in a lab after college and trying to decide if grad school was in the cards for me.
This book is based on the true story about the labs that were instrumental in isolating the first oncogenes in the early 1980s. It is a great science story for those who have never heard it, and also gives a very good idea of what life in the lab is like at all levels. It also emphasizes what was said recently in Twiv 161, that life in the lab is very much about social interpersonal interactions, for better and sometimes for worse.
I don't know if this book has ever been picked before, but if not, I would highly recommend to all as a good read.
I discovered your podcasts a few weeks ago and have really been enjoying them. I toyed with biology as an undergraduate and I love it. But I ended up in business.
I just learned of the Science Exchange today and thought you might be interested given your interests in uses of the internet in the interests of science: