Jim writes:
Please be nicer to Dickson.
Johannes writes:
Dear Vincent,
I heard you mention Kevin Folta a couple of times on your various podcasts, but you do not seem to be very familiar with his situation. Especially when I heard you mention in passing “Folta is funded by Monsanto, right?” the other week.
The two of you are actually not very different. You are both public advocates for science. I therefore think you should make yourself more familiar with his case. Especially since you also speak out about the pseudo science around viruses like vaccines and HIV denialism in your shows. If the antivax crowd where as vicious as the anti GMO people they could also target you with FOIA requests claiming you to be in bed with “Big Pharma” and then while reading through thousands of your emails take and represent some of them out of context.
A good way to start would be to listen to Folta’s podcast episode 13 where he explains what is going on and his alleged ties to Monsanto (http://www.talkingbiotechpodcast.com/?p=130).
Otherwise I love all of your shows, thanks a lot for the many hours of entertainment you have provided me.
Kind regards,
Johannes
Yegor writes:
Dear TWiV hosts,
Let me provide some thoughts on proviruses, sterilizing immunity, and abortive infection.
The difficulty with HIV (or SIV) infection is not the formation of the provirus per se, but the fact that some proviruses end up in reservoirs, where the virus gets preserved and then can come out and re-seed the infection. There’s still some controversy about the exact nature of those reservoirs. These could be memory CD4 T cells, or stem-like cells from which CD4 T cells originate, and some people believe that follicular T helpers in germinal centers serve as such reservoirs because they are shielded there from CD8 cells (which are not allowed to enter B cell follicles). Whatever those long-lasting reservoirs are, the underlying biology of the infected cells is the main reason why HIV and SIV infection persists in the face of antiretroviral therapy or effective immune response (observed in elite controllers), not the formation of a provirus. The formation of the provirus may help in this process if for some reason the provirus is not being transcribed for some time and then gets re-activated.
However, if a CD4 cell is infected and then killed by T cell immunity, then it does not matter whether the provirus was formed or not. Many infected CD4 cells will die on their own despite the formation of a provirus.
If a vaccine boosts the immunity and leads to efficient clearance of infected CD4 cells, then you may see a situation where the virus comes in, starts replicating, but then gets suppressed or completely eliminated. In the past, TWiV covered the CMV-based SIV vaccine developed by Louis Picker and co-workers. To remind you, what he observed was robust systemic replication of SIV, followed by complete suppression of the virus in 50% of vaccinated animals. At the time, he saw the virus persisting in these animals. Since that episode, he has shown that over time the virus gets completely eliminated from the body. According to him, the most sensitive test for elimination of the virus is to transfer a large amount of PBMCs from the animal in question to a new non-vaccinated macaque. If the virus is there in even tiny amounts, it will grow out and establish infection.
Finally, I’m not completely certain that the authors saw two distinct types of protection – the difference between sterilizing immunity and abortive infection is not black and white. Viral replication can be very local and very short, so that you will not be able to detect it by looking for viral genomes in the blood. Sometimes you may detect such cases by detecting immune responses to viral proteins that were not included in the vaccine. I don’t have access to the paper, so don’t know how extensively the authors looked for such secondary signs of infection.
Hope this was helpful,
Yegor
P.S: I’m glad to hear that Vincent followed my recommendation and started listening to Hardcore History. Spreading the word about great podcasts is the best way to show your appreciation (I’ve been advertising TWiV to lots of people, hope some of them picked it as well).
Yegor Voronin, PhD
Senior Science Officer
Global HIV Vaccine Enterprise
Ebony writes:
Hello TWiVers!
I’m a PhD candidate in Michele Kutzler’s lab at Drexel college of medicine. We’re a DNA vaccine lab and I just wanted to answer your questions about electroporation (EP). The vaccine plasmids themselves are given intramuscularly by regular injection. The Innovio probe has three small probes which are then inserted around the injection site and the charge is delivered as 3 individual pulses of milliseconds, separated by a few milliseconds, it takes maybe 4-5 seconds. As far as pain, I have poked myself on probes and they do hurt, about a much as a needle, the EP is so quick it probably only hurts for a short time. Hope this helps!
Jens wrote:
I have just returned from this year’s ICTV Executive Committee meeting in London. There are some really exciting developments lately, starting with the question of what a virus is (the EC just accepted classification of “satellite viruses” and “virophages” which was based on a proposal I was part of) to classification of segmented (!) non-enveloped (!) viruses in the Mononegavirales (dichorhaviruses and varicosaviruses) and the establishment of several new mononegavirus families and free-floating genera based on sequence data alone (and the problems that come with that). We are also in process of laying the ground work for reorganizing the bunyaviruses (to include emaraviruses, tenuiviruses, and Mourilyan virus, and most likely arenaviruses!) and there is more and more consensus for the need of higher taxa (phyla, classes etc.) to represent the phylogeny of viruses more adequately. And of course we ended up bickering over naming conventions and what makes sense, and whether species names should not follow the classical Linnean structure etc.
Hearing your repeated mentioning of (and sometimes justifiably complaining about) the ICTV on TWiV, I think it would be great fun and very useful for the community to have a taxonomy TWiV discussing these issues and other fun things, such as paleoviruses or what to do with TSA virus sequences and whether transposons should be considered viruses and so on. I’ll swear I’ll make it fun by talking about T. rex (classified without a living “isolate”!), centipedes (no, none has 100 legs and yet the name is just fine) etc.
You see, I am anxious to get back on your show (and I am on a mission). We could even call Welkin out (as revenge for him putting me on the spot during my TWiV episode) and ask him why Jembrana disease virus is not yet classified (he is the chair of the ICTV Retroviridae Study Group). 🙂
Amy writes:
Dear Dr. Vincent Racaniello,
I am a researcher in a food lab in the DC area, and one of my projects involves virus sequencing. I really like your “virology blog” “virology 101” and learned a lot from you. I am not sure about the exact definitions of virus “strains, isolates, variants, genogroups, genotypes, types, sub-types, and quasi-species”, could you please help me on this question? Thanks very much!
Best wishes,
Amy
Rockville, Maryland
