I couldn’t find a HAVE YOU HUGGED YOUR PHYTOPLANKTON TODAY? bumper sticker. HAVE YOU THANKED A DIATOM TODAY? bumper stickers I did see in two designs:
It all too very often seems that NJ isn’t a State, but a punchline instead. Indeed, I didn’t think that there was much of anything to be proud of here — with the exception of Merck making possible the hope of the eradication of River Blindness. That was before TWiV 562.
Thanks go to you and your colleagues for putting NJ on the map in a good way.
Dear Vincent and the Gang,
I imagine thousands of people from Regeneron emailed you about the way antibodies to Ebola were derived at the company. But just in case the number is a bit lower, here’s the link to the paper describing the VelocImmune mice: https://www.pnas.org/content/111/14/5153 The mice are genetically modified to replace the mouse Ig heavy and kappa light variable region with that of the humans. All antibodies in these mice carry fully human Fab regions and mouse Fc region, so it’s very easy to “humanize” them after isolation.
Also, here’s my thoughts as to why the term “quasispecies” is getting replaced with “swarm”. Quasispecies were introduced by Eigen back in the 70s to describe early evolution of life on Earth and then later expanded to viruses by Domingo, Holland and others. However, originally the term was quite specific (in fact, it was defined in mathematical terms in population genetics models) and was used to describe a situation when a collection of closely-related clones has a different biological behavior than any single clone. It was argued that in such cases in evolutionary terms, the quasispecies serves as the unit of selection, not individual clones.
Later, virologists started using the term quasispecies to refer to any collection of closely-related viruses, especially to the rapidly-mutating RNA viruses, which often exist as swarms of mutants. The old guard was not happy and often corrected the “incorrect” use of the term. Just to give one example, in this article by Wilke (https://www.ncbi.nlm.nih.gov/pubmed/16107214), he writes: “virologists in general have frequently used the term quasispecies inappropriately”. I guess the pedants won and folks began to use “swarm” rather than “quasispecies” to avoid hearing for the hundredth time that they are using it wrong.
Thank you for the excellent podcast, I listen to you every week on my long commute to work.
Yegor Voronin, PhD
Chief Operating Officer
Worcester HIV Vaccine
Hope everything is going well.
I am listening to your most recent podcast episode. In your search for the REGN mAb combo you found the clinical paper, but you missed the preclinical paper, I am attaching it here. We are describing the development, properties and most animal studies with these antibodies (attached).
Talk soon! https://www.ncbi.nlm.nih.gov/pubmed/29860496
This email is sent from the beautiful capital of Sweden, Stockholm. It is way overdue, but better late than never…
Some time ago, a coworker of mine here at the Public Health Agency of Sweden asked me, “Do you know of this podcast called This Week in Virology? It’s really good!” I looked at her and smiled, “Do I know of TWiV? I personally know two of the people in the podcast, Rich and Alan.” I could tell she was super impressed.
I then forgot about the conversation until I went to a meeting last year, The Smögen Summer Symposium on Virology. I think you know which meeting I’m talking about but for them who don’t…..Every year the Swedish Society for Virology have a meeting on a small island called Smögen on the west coast of Sweden. It is a really good meeting with both national and international participants, great science and the best seafood ever. Well, I can’t really back up the seafood statement since I’m a vegetarian, but the meat/fish eaters seem happy. Anyhow, at the end of the session about vaccines, the speaker put up a picture of TWiV episode 496 and said, “If you want to hear more about vaccines you should listen to this really good podcast and their vaccine episode. It’s about 40 min long.” I could not be quiet and raised my hand, “You’re absolutely right, it’s a great podcast but 40 min? Come on, they haven’t even finished their weather reports in 40 min!” After that the majority of the audience started to talk about your pod. It turned out that most of the people in that room knew of, or listen to TWiV! So you don’t just have one fan (me) in Sweden, but many!
How I know Rich and Alan? I did my Ph.D at the University of Florida and met Alan through Dr. Condit. Rich suggested I invite Alan as a speaker for our Career Seminar Series. Each month we invited a speaker with a Ph.D in biomedical sciences to talk about their careers. The purpose was to expose us, the students, to other options than the academic/professor route. Alan spoke about being a science writer and his talk was very appreciated. Mostly because it was an interesting talk, but also because he was honest with the pros and cons of the job as a science writer. So thank you again Alan for your seminar and advice.
As a microbiology/immunology grad student at UF, Dr. Condit was one of my teachers. One of the first encounters I had with him was when I just had gotten the smallpox vaccination because I rotated in a lab working with vaccinia. Dr. Condit was very excited about this. Me, not so much (since I got a bad scar from it). Even if I did not share Rich’s enthusiasm for that particular vaccination, I appreciated all other discussions we had. Dr. Condit’s passion for science and virology always shined thru, which was very refreshing and inspiring. I don’t know if I ever thanked him for that? If not, thank you Rich and thank you for coming to my defense even though I chose HIV over pox viruses ;). As a matter of fact, not too long ago I actually got proof that Dr. Condit has inspired others too….I was discussing viral vectors for vaccine delivery with one of our English collaborators and pox viruses came up. “I know a pox guy, Rich Condit!” My colleague looked at me, “you know Richard Condit?!” I explained how I know Rich and asked how he knows him. “O, I don’t know Dr. Condit, I only know ABOUT him and his work. Very impressive and inspiring.” Now my colleague asks about Rich every time we meet.
So in conclusion, the podcast and you are all very appreciated amongst virologist/immunologists in Sweden and England and I hope to see as many of you as possible in Smögen this year! It’s time for a second road trip in Sweden Rich!
Ps It’s 4 pm and 17 degrees Celsius outside. Not the best Swedish summer day but it will be better in August. I promise 😉
Thanks, Rich, for channeling my thoughts about the Ars Technica article and Ted Talk. “Get a load of this Bozo” about covers it.
I had thought that the old ferret arguments had settled down, but instead seem to be entrenched. OK insufficient reporting. Again.
Reid’s fantasy scenario of some lab creating a truly terrible disease as an experiment or weapon is however one that people can be rightly concerned about. Reid also believes, as he says, ‘synthetic biology’ “could be the greatest boon to humanity in all of history”.
He has good ideas and some missing info and could profitably spend some time talking to a greater variety of scientists to lower the BS level.
Great podcast as usual gang. Many thanks.
From the discussion of measles virus budding through the apical surface of lung epithelia, I can’t help but wonder about the biophysics (?) of that virion release. When those particles (or any virus shed through airway) are pinched off, it’s not like they are now floating in a bubble/aerosol droplet on their own, but in a layer of mucus, right? I believe I have read that the deepest recesses of the alveoli are warm, wet places. I imagine that the force of coughing could dislodge mucus with the virions in what become aerosol droplets of varying sizes.
Thanks for a great discussion of the hepatitis delta paper in TWIV-552 – to me one of the most exciting papers this summer. Fascinating that HDV can utilize not only HBV but also other viral envelopes to package its genome! Will be interesting to follow what real life examples will be found in the future.
As a virologist passionate about hepatitis viruses, I couldn’t help stumbling upon your alphabet list of hepatitis A through G. Someone (Rich Condit?) saved it a bit by explaining how hepatitis F was a fluke. Unfortunately, here like many other places “G” was still mentioned as if it was a hepatitis virus (the course book for medical students at our university is no better!). In the excitement over identifying novel hepatitis viruses in the 90s, conclusions were perhaps drawn a bit prematurely and unfortunately the name sticks. It happens to be that “HGV” is not liver specific, it does not cause hepatitis, and most evidence suggests that it doesn’t even replicate in the liver. Rather, it is a rather interesting virus that flies under the radar and can cause persistent infection with no clinical disease, belonging to the genus Pegivirus within the Flaviviridae family. When discovered in parallel in two different studies, one study termed the virus HGV, while the other termed it GBV-C. Shortly before that, two other viruses of the Flaviviridae family had been discovered after 11 passages (!) in tamarins of an acute phase serum during hepatitis from a surgeon with initials G.B. These were termed GB virus A and B, although it to date remains unclear whether they were ever in the original human sample. Because of phylogenetic relationship, in particular to GBV-A, and although completely unrelated to the G.B. sample, the new human virus was named GBV-C. To avoid confusion, and perhaps because the two original names were equally inaccurate, it was recently renamed “human pegivirus” HPgV.
In the same episode, you end up talking about horses and liver disease, and there I couldn’t help noticing a very convincing reply from Vincent when the question came to whether hepatitis viruses in horses are known. Not too well known, I would say, because we are really just beginning to understand what’s going on there. Despite infectious liver disease in horses, “Theiler’s disease”, has been known for 100 years. Infection of horses with the closest relative of HCV, “non-primate hepacivirus” or “equine hepacivirus”, NPHV/EqHV, discovered by Amit Kapoor in 2011, indeed resembles HCV infection a lot. It is a liver specific virus that causes hepatitis (as defined by infiltrating lymphocytes; see e.g. Scheel et al. 2015 PNAS) – but perhaps not much more than that. In contrast to HCV, most NPHV infections in horses do not become persistent and are not linked to any clinical disease (e.g. Pfaender et al. 2015 Hepatology). The question is whether the lower fraction of chronic infections can cause liver disease in horses, and case examples begin to suggest that it may. In another story, strikingly similar to that of HGV, another pegivirus “Theiler’s disease associated virus”, TDAV, was linked to an outbreak of acute serum hepatitis after administration of botulinum antitoxin in horses in Nevada in 2013 (Chandriani et al. 2013 PNAS; biologicals given to horses are often produced in horses without subsequent purification!). Given what I mentioned above, that pegiviruses normally are not associated with disease, this came as a surprise. Further, no other TDAV cases could since be identified in horses with liver disease. Surprisingly, collaborators of ours, Tom Divers and Gerlinde Van de Walle at Cornell and Amit Kapoor at Nationwide Children’s, instead found a novel parvovirus in almost all horses with unexplained (infectious) liver disease tested (Divers et al. 2018 EID)! Looking back at the Nevada outbreak, it turned out that all affected horses and the responsible lot of antitoxin was positive for both viruses – TDAV and the parvovirus! It just happened to be that viral discovery had only been done on RNA – not DNA… Together, we are currently finishing a study on TDAV showing that this equine pegivirus does not lead to clinical symptoms and evidence for negative strand RNA (replication) is exclusively found in the bone marrow. This tropism happens to align well with a recent study on simian pegivirus (Bailey et al. 2015 Sci Trans Med) and older case reports on GBV-C.
So for humans, we can agree on hepatitis A, B, C and E (I belong to those who wouldn’t consider delta a ‘real’ virus – but that’s a completely different discussion). For horses, we’re probably looking at a parvovirus, perhaps EqHV/NPHV, and who knows which others…
And yes, one of the two microRNA-122 inhibitors tested in clinical trials for HCV indeed is pegylated! This does increase its stability, and it is nothing less than fascinating that several patients obtained virological cure by a single shot (!) of this inhibitor (van der Ree et al. 2017 Lancet) – a disease that just a few years back could often not be treated despite yearlong therapy with severe side effects.
Thanks for a great show, and looking forward to seeing you next week in Smögen!
P.S.: Sorry for the length of this email – it was my intention to keep it short!
Troels Scheel, PhD
Copenhagen Hepatitis C Program (CO-HEP)
Department of Immunology and Microbiology,
Faculty of Health and Medical Sciences,
University of Copenhagen &
Department of Infectious Diseases,
I have been using Zome Tools to build viruses in my classes. They are great for building icosahedral shapes.
https://www.zometool.com/shop/ (One picture all shows my 3D printed viruses)
Thanks for all the TWiX podcasts,
Department of Infectious Diseases
Department of Population Health
University of Georgia