Jean-Michel Claverie writes:
Roaming on the net, we discovered yesterday that you dedicated a whole episode of TWiV (440) to Noumeavirus. Thanks for contributing to our fame ! 🙂
Even though you made fun of me and Chantal about our style (“strict” embargo, circumvolution, etc …) we were impressed by the details in which you went through the paper. Good job. I wish our students/postdocs would go into such details too.
However, some of the questions you asked were actually answered in the …. supplementary materials (such as messenger polyadenylation). As for tracking the viral DNA inside the host cell, we tried (using EdU) but had no success yet. Same in expressing other GFP-tagged proteins. This is unfortunately tricky in the Acanthamoeba system.
As mentioned by Richard Condit, such experiments have been attempted with Poxviruses for dozens of years without success …. so give us more time.
As for the recent paper on the new “super giant” Klosneuviruses authored by Schulz et al (with Koonin), I (and others) have huge reservations about it, and I will probably post my comments about it on PubPeer and/or pubmed in the near future. Basically, I don’t believe in viruses until I have is isolated in a tube. I believe ICTV does agree with me in not taking for granted metagenomic assemblies as good enough evidence for “new” viruses, especially “revolutionary” ones.
Thanks again for your interest in our research,
Bien amicalement and meilleurs souvenirs,
Jean-Michel & Chantal
I just finished listening to TWIV 440 where you discussed the transient disruption of the nuclear integrity by the giant Noumeavirus. Rich mentioned that he thought the evidence was not conclusive as to rule out the possibility of the viral DNA first entering the nucleus to initiate transcription. This reminded me of the entry process of two small DNA viruses, SV40 – a member of polyomaviridae (with a capsid of 50nm) and MMV (minute virus of the mouse, a member of parvoviridae with a capsid of ~26nm). Both of these viruses transiently disrupt the nuclear envelope integrity during their entry into the nucleus. Similarly to what was described for Noumeavirus, these disruptions consist of transient morphological changes in the nucleus and increased “leakiness”. I’ve attached the relevant papers.
Keep on the good work,
Nir, a postdoc in gloomy Chicago, where the weather is currently 7 C, cloudy and nowhere near as nice as back home in Israel…
I am writing this letter in response to Allison’s letter on TWiV 440 regarding adverse effects of vaccination. Since Alan seems to think that anecdotes are more likely to attract the attention of people who are opposed to vaccination, I would like to offer a few of my very own personal anecdotes.
Anecdote Number 1: I had severe cases of the flu two years in a row, in 1998 and 1999. I remember those years exactly, because the illness was so debilitating that I remember wishing for nothing more than good health. Both times the illness lasted a total of two months, mostly due to the bronchitis that developed as a secondary infection. I will never forget the misery, the pain, and the feelings of hopelessness and uselessness because I just wanted to feel healthy and productive again. Since 1999 I have been getting a flu shot every single year and since then, I have not had the flu. I have been around plenty of people who had the flu, especially family members and co-workers who refuse to be vaccinated. This year in particular was a very difficult flu season, with lots of co-workers missing work repeatedly for extended periods of time. I however, still did not get sick. If I did get infected with influenza virus in the past 18 years, the illness manifested itself with minor aches and pains which maybe lasted a total of 1-2 days, and after which I felt completely healthy again. This is consistent with reports indicating that even if the flu vaccine fails, in most cases, the severity and duration of symptoms are significantly reduced. (Sorry, I used a statistical term… I just can’t shake the scientific approach…) 🙂
Anecdote Number 2: My children, who have also received the flu vaccine every year of their lives, including during their in utero season, have never had a full blown case of the flu. If they did get sick, the illness lasted a total of 1-2 days, and they NEVER developed any respiratory complications. In addition, they are, at their respective ages of 1 and 3, completely up to date on their vaccines, and they have never had any adverse effects from their vaccinations, besides the slight elevation in body temperature that sometimes occurs the night following vaccination. They have also never had any other serious infections. They have never had the measles, mumps, or rubella. They have never had polio, diphtheria, rotavirus infection, hepatitis B, pertussis, tetanus, bronchitis, pneumonia, or chickenpox. And because they haven’t had any of these diseases they haven’t passed them on to other children. You know what else they haven’t had? Smallpox. And you know why? Because Smallpox was eradicated with a very effective vaccine more than 35 years ago.
Anecdote number 3: I did NOT receive the MMR vaccine as a child, and consequently I had a full blown case of the mumps at the age of 7. I remember the illness distinctly, as I was bedridden for at least two weeks with extreme pain in my salivary glands. I specifically remember the pain as I tried to lift my head off the pillow, which you have to do every time you turn in bed, or get up to eat, or go to the bathroom. Even though I obviously eventually got better, this disease left me deaf in my left ear… 85% deaf to be exact. While it is not the end of the world, and I am perfectly healthy otherwise, 85% deaf on one ear means you can’t hear sound in stereo, so you often don’t know which direction sounds come from (e.g. elevator dings, people calling your name in crowded places, car horns, etc.). You’re also a nuisance to the people around you, as you’re constantly asking them to repeat themselves. You listen to music and audio really loudly, once again annoying those around you. You always watch movies with subtitles on, in order to keep the volume at a reasonable level, so as to not annoy those around you. You may not hear people when they’re talking to you from the affected side, especially in environments with the slightest background noise. If people don’t know you or about your disability, this can create some social awkwardness. Whispering anything into that ear is completely out of the question, as is telephone use on that side. Long story short, it is a major, MAJOR nuisance. It may even be a hazard at times.
What I have noticed with this entire anti-vaccine sentiment is a very unfortunate glorification of the old days, because life was allegedly so much simpler and “less toxic” back then. But that is not so. People routinely lost children to simple bacterial infections. Women routinely died in childbirth. Surgery of any sort was always very risky. My own distant family history is rampant with infant, child, and adult deaths from pneumonia and complications from various other bacterial infections. Why do we forget that? Maybe we need to remind people about science history.
Anyway, keep TWiVing, dear TWiVoners.
I guess one could say that the AHCA bill is the kind that makes you sick.
Good afternoon Beacons of Viral Education,
Episode 424 was a contemporary favorite. I’m writing to win but also in regards to the discussion of prion diseases. In episode 424 it was said that vCJD prevalence was rare in the population but I wanted to ask– is it? The fact is, given the potential long duration of the pathogenesis of this disease AND the fact that we do not routinely test the expired for presence of vCJD unless they were symptomatic, I think it’s a pretty big assumption that it’s rare! I think the newly developed assays are going to be extremely valuable in contributing to the prevalence numbers in given populations. Perhaps the rate is low but we will hopefully find out once the non-invasive assay is refined and approved. Even then the sample size may remain small because without a cure or therapy people may not elect to be tested.
In regards to the containment question–thank you Alan for asking!!!! As a Biosafety professional it makes me heart sing to hear such important researcher-safety questions raised.
In my job we discussed this very issue of appropriate handling practices involving human brain tissues with microtomes or cryostats. Considering the paper (Haybaek et al
I thought you’d covered this last year or before?) that demonstrated transmission of prion disease through the aerosol route, it seemed unnerving not to play it safe and recommend containment for this activity. Especially knowing that the true prevalence of vCJD in the population is unknown!
In any event, I loved the discussion and as a previous field research technician responsible for removing deer brain stems with an apple corer to test for CWD, prions have been an interest of mine since the days of my undergraduate career.
I hope I’m #17 because I love the topic of infectious diseases as much as I love traveling to far flung places and eating weird things. The way I look at it is, the cultural, social and potentially medical adventure I may go on will add to my varied and interesting life story either way and worst case maybe make for a interesting epitaph!
In any event, I love the show and wish there were more time in a day, week etc. so I could consume all episodes of the whole suite. I especially love listening to such provocative content when even NPR nauseates me for reporting on (and I realize they have to) the flagrant stupidity of the newly appointed administration (you don’t have to repeat that aloud!).
PS In RI, it’s 42F and 59% humidity with a gale warning in effect
PPS I wish Blue Apron had a holiday giving program where you could order meals for families in need (food deserts!)
To the wonderful faculty of TWIV,
Recent mention of Dr. Richard Kessin’s book, The Famine of Men, whose main premise is that a virus has made all males sterile, while not affecting women, brought to mind the late crime novelist P.D. James’ uncharacteristic foray into science fiction, the dystopian novel, The Children of Men.
The James story is set in England in 2021 and its premise is that due to universal infertility of unidentifiable etiology, no babies have been born since 1995. One female who is a member of a dissident political group finds herself pregnant and the plot revolves about the small band’s flight for survival.
The early pages of the novel contain the author’s well crafted take on Western’s science’s achievements which I think you will enjoy:
“We are outraged and demoralized less by the impending end of our species, less even by our inability to prevent it, than by our failure to discover the cause. Western science and Western Medicine haven’t prepared us for the magnitude and humiliation of this ultimate failure. There have been many diseases which have been difficult to diagnose or cure and one which almost depopulated two continents before it spent itself. But we have always in the end been able to explain why. We have given names to the viruses and germs, which, even today take possession of us, much to our chagrin since it seems a personal affront that they should still assail us, like old enemies who keep up the skirmish and bring down the occasional victim when their victory is assured. Western science has been our god. In the variety of its power it has preserved , comforted, healed, warmed, fed and entertained us and we have felt free to criticize and occasionally reject it as men have always rejected their gods, but in the knowledge that despite our apostasy, our creature and our slave, would still provide for us; the anesthetic for the pain, the spare heart, the new lung, the antibiotic, the moving wheels, and the moving pictures. The light will always come on when we press the switch and if it doesn’t we can find out why.”
Thank you all for the wonderful podcasts. May you keep the lights on in good health for many years to come.
Ted Splaver DMD
Adjunct Faculty, Department of Oral & Maxillofacial Surgery, College of Dental Medicine, NOVA SE University, Davie/Ft. Lauderdale, Florida
Hi TWiV folks,
First time writing in after listening for about a year and a half, and hoping I’m the lucky winner for the book contest! I fell behind a few weeks so I was pleasantly surprised while listening to this past sunday’s episode to hear you still hadn’t reached #27. Hope I’m it!
While catching up, I was excited to find the previous episode (#429) was taped with a group from the University of Wisconsin. I am from Madison originally and graduated from UW in May of 2014. During my last two years I was lucky enough to be an undergrad in Andy Mehle’s lab (influenza transmission) and it’s great to hear about all the cool work going on in virology back home.
I also just wanted to say thanks for all you do. Your podcasts help me get through my long days as a lab technician while I patiently wait for my boyfriend to finish up his PhD in microbio. Soon it will be my turn to go to school (applying to virology PhD programs this fall!) and TWiV keeps me up to date with the ever-evolving field of virology. Thank you for the intelligent discussions and laughter!
PS: In case you are still polling, I do listen all the way to the end of the episode!
It seems like every week I have an idea to write you about but never get around to it (do you have a round tuit, to spare?).
Anyway, this topic really strikes home so I am extra-motivated to contribute.
With respect to your discussion of potential protein folding disorders that have non-neurological consequences (twiv 431), there is at least one class that I am personally aware of. Desminopathies are caused by mutations in the gene that encodes the scaffold protein desmin, a component of the muscle contractile apparatus. At least in its autosomal dominant forms, desminopathy results in the accumulation of mis-folded aggregates in muscle cells that eventually produce what is called myofibrillar myopathy.
People with desmin mutations can present with muscular dystrophies that have varying ages of onset and rates of progression. The one in my family has a fourth to sixth decade-of-life onset, usually appearing as a limb-girdle-type dystrophy, affecting use of the legs and, more slowly, the arms. Loss of ambulatory function sometimes may not occur until the eighth decade. Perhaps the slow progression arises because “garbage disposals” in cells can deal with the mis-folded aggregates until they become too abundant, or the cells get “too old”.
Desmin is particularly abundant in cardiac muscle, and desminopathy can manifest as both cardiomyopathy and conduction disease. Sometimes the consequences of the latter, before any skeletal muscle issues surface, are the first sign: sudden cardiac death can result.
Other organ systems in the body that depend on muscle function also can be affected.
I wonder if the cellular turnover (or lack of same) in a tissue is critical for whether it’s likely to be affected by a protein folding disorder. Cells that turn over rapidly might not allow accumulation of the aggregates. On the other hand, cells like neurons, and maybe muscle when there isn’t a lot of turnover, might be more susceptible. If the hypothesis is correct, one might expect exercise to slow the progression. I don’t think the relationship between desminopathy progression and exercise has been examined. This is counter-intuitive, don’t you think? Because you might predict that constantly breaking down muscle and trying to rebuild it in a person with a muscle disease would be deleterious, not favorable.
So much for this diversion.
It’s currently 63° (17°C) with cloudless skies in Hershey, Pennsylvania. We’re expecting 1-3” of snow after midnight. Don’t you just love March in the temperate zones!
Virology Rules and you folks are the Court Royale!
David J. Spector, Ph. D
Professor Emeritus of Microbiology and Immunology
Penn State Hershey
Jon Yewdell writes:
- Many thanks to you and the TWIV crew for another fantastic year of podcasts.
- Now for the pedantic comment. In TWIV 422, there seemed to be a consensus (@ 43 min) that the CNS is a dead end for viruses (in this case Zika). Rabies provides a clear example where CNS infection plays a critical, albeit indirect role in virus transmission, since the increased physical aggression driven by the virus (which can even be seen in humans, though not in this gruesome video https://www.youtube.com/watch?v=-moG6JDmJdc ), fosters transmission through biting, as viral replication peaks in the salivary glands. It is plausible that CNS infection can foster transmission of mosquito borne viruses through numerous mechanisms. These include changing host behavior (making the patient less likely to avoid/prevent mosquito bites, thus favoring transmission), modulating the immune response (the CNS plays an underappreciated role in systemic antiviral immunity; see attached papers for participation of sympathetic nervous system in flu immune response), and like herpes viruses, infecting nerves that deliver the virus to barrier tissues (e.g. skin, mouth). The TWIV panel can probably come up with other potential mechanisms in a blue-sky discussion.
- A proposal. How about a father son TWIV episode? Would be a first? My son Teddy is a post-doc at Sloane Kettering. Though a virologist only by inheritance, he is working on B cell responses, and using flu as a model antigen (we just published our first co-authored paper). This could be really fun, and provide a new perspective on scientific careers.
- Very best wishes for the new year!
Long time listener, first time caller!
I have read about extracellular morphological changes in archaeal viruses but can’t find such a technique in any other domain. I thought I would ask the experts.
Spreading the TWiX world here at Stony Brook,
I’ve been thinking of this in the letters to TWiV 425:
“My question for you and your many guests is what are the anomalous and unexplained phenomena in virology today – the facts and circumstances that defy explanation by the standard model?”
# # #
Before giving an answer, I’ll have to be very confident of knowing “the standard model.”
A few things did come to mind. If memory serves me correctly here
Sam Walton notes that in the early days of computer generated sales reports, He’d go into the office at a quiet time. (2 am Saturday morning?) He’d place the stacks of big fanfold printout paper on the conference room table and then walk up and down looking for outliers. When he found a store doing better with some item, Sam Walton would call the manager to ask what they were doing.
Somewhere I read that the SEC “trolls” for insider trading by casting out an algorithm for every stock quote to swim through.. The software nets behavior that does not mirror the market, If there’s later on some public announcement that explains the previous up or down movement, the SEC considers investigating.
Clearly, insight and intuition will be self-seeding in the garden of the prepared mind. Even so, might there be devised automated nets for fishing in the growing waters of metadata?
And, before anomalies can be caught, the trend needs to be known.
“’Information overload equals pattern recognition.’ At instant speed the hidden becomes plain to see.”
Dear TWiV consortium,
First, please forgive my formatting, for I am not much of a letter writer. Second, my name is Brandon from Denver Colorado, a long-time listener who has only emailed once. Even that was a halfhearted attempt to win one of your contests. As for the weather right now I look out from my desk to a somewhat overcast 18 C day, expecting snow over the next two days. We are long overdue for our March snow storm but I enjoyed the ~22C weather while it lasted.
I write for no particular reason; a large part of it is the admiration I have for you all, part of it is that I have eked out just enough time to put together an email for you all, something I’ve wanted to do for a long time. My favorite episodes are TWiV 373 with Dr. Younger and TWiV 395, The Cancer Thief, I have listened to those episodes many times over and have stopped me from remaining current. As much as I love the usual gang, your interviews with other distinguished virologists tend to be especially riveting.
Now a little about myself (the least interesting part, I assure you). I am a high school dropout from a family of high school dropouts that eventually realized school is cool. I went back and finished my high school diploma and I am now in my final semester as an undergrad, earning a degree in Biology with a minor in chemistry. I am proud to say I will be going to the University of Florida to pursue a master’s degree in microbiology this upcoming fall, something that has never felt real or possible. I often have felt like quitting everything, but the Good Doctors of TWiV help keep me motivated. Through your constant humor (or “humor” from Dickson), stimulating discussions and continued desire to learn. Thank you all for the work that you do.
Tiredly yours, Brandon
P.S. I do find Dickson quite funny and appreciated his attempt at the OVER 9000 meme. I often find myself rolling my eyes with a smile on my face after one of his puns.
P.P.S There is a Regional Conference for ASM on April 15th that I am excited to attend and I thought others might be interested.
P.P.P.S I miss Rich.
Hi Vincent et al,
I just read this brilliant editorial view from Richard Horton, and I think it would make a great listener pick, and deserves wide circulation for pinpointing one of the most insidious and damaging trends of our time.
Who knows: it might even help him see we don’t just like harassing him over PACE! 😉
“Difficult truths about a post-truth world.” Lancet 170401
This is a great piece from Richard Horton, editor of The Lancet. It should remind us all that, while Brussels may seem to have more of a ‘green’, ‘socially responsible’ face than our own rabid government, the EU exists for the explicit purpose of promoting business, and is run by the business lobby, for the business lobby.
Especially note how the principle of truth of scientific objectivity, is being encouraged to be thought of as just another biased view from vested interests. This lobbying angle literally is capable of destroying worlds.
All the best,