Lisa writes:

Dear Dr. Racaniello,

I just finished watching your podcast,  TWiV 373: The distinguished virology career of Julius S. Youngner.

It is an absolutely wonderful conversation, thanks to your skills as an interviewer and my Dad’s as interviewee.

Thank you so much!

Lisa Youngner

(Juli’s daughter)

Nathan writes:

Dear Professor Racianello,

Thank you for TWIV #373 and the timeless interview of Professor Julius Youngner. This episode will join my triumvirate of favorite TWIV episodes of all time, the other two are TWIV #277, Eugene Koonin, and TWIV #197, Philip I. Marcus. I was struck by the career parallels between Prof. Youngner and Prof. Marcus, respectively. Both were touched by the Manhattan project (uranium inhalation: Leo Szilard mentoring). Both made pioneering contributions to cell culture technique still relevant and in use today (trypsinization: feeder cells). Both encountered nasty conflicts between large egos and scientific ethics (Salk/Cutter incident: Puck not crediting Szilard for feeder cell idea).

Keep up the great work!

No TWIV letter is complete without the weather…it’s 50oF (10oC) and cloudy in Chapel Hill


Anthony writes:

“AUSTRALIA’S  waterways could be rid of carp by next year as moves to import a virus targeting the pest gain ground.

Scientists at CSIRO have wrapped up almost a decade of testing to prove the bug kills only the so-called “rabbit of the river” clogging the Murray Darling Basin, The Weekly Times reports.

Applications to introduce the virus in Australia are now being submitted while an unlikely alliance between ­industry and environmental groups, including the National Irrigators Council and Australian Conservation Foundation, support the measure.

“This single initiative could be as important as myxomatosis was to halting the rabbit plagues,” NIC chief executive Tom Chesson said.

Lenn writes:

Fewer Cruises Rocked by Gastro Illness Outbreaks

Michelle writes:

Hey TWIVers,

The next semester of nursing school is starting up for me on the 20th of January, and I’m super excited because one of my classes is Maternal-Fetal care. Our teacher (in a fit of brilliance) has us fill out an “admissions ticket” where she gives us a topic, and we have to go do research before we’re permitted to attend the day’s lecture. The first one we received was to gather basic information about the Zika virus, the implications surrounding exposure during pregnancy, and the current events about ZIKV, lack of vaccines, and the outbreaks that have been occurring in the Southern American countries.

I just happened upon a NYT article that was touching upon what they say is the first confirmed case of microcephaly correlated to prenatal exposure of ZIKV. The article is a bit scant on particulars (they say that the CDC confirmed the presence of ZIKV infection in the mother during pregnancy, but don’t spell out how that was done), but I thought that you guys might be interested in seeing what is being published outside of CDC and research literature (which is the only arena in which I’m seeing ZIKV being talked about). The link is here:

I definitely plugged episode 368 (Infected, you will be) to the rest of my nursing class, and I’m very much looking forward to seeing what the other students have found in the way of information surrounding the clinical care surrounding ZIKV and pregnancy. It looks like Brazil is throwing their

Best Regards,


P.S. The weather here today (in Fayetteville Arkansas) is a balmy -6º C with clear skies and a mild wind. Later today should be partially cloudy, and we might even get to thaw out our toes when the high gets to a balmy 3º C.

As a future family practice DNP and midwife, you all are an invaluable treasure trove of information and are a great way for me to stay aware of the current research going on outside of the realm of nursing research.


David writes:

Hi, twivniks,

I enjoyed the discussion of HCMV UL138 and its role in transcription control of HCMV gene expression in TWiV 372. The mechanism underlying the lysis/latency switch in herpes viruses is a long term interest of mine and it’s nice to see the progress on identifying the mechanisms of a likely transcriptional component of that switch. Whether that component is sufficient or only necessary for a functional switch is difficult to resolve genetically from the systems at hand, at least for HCMV, because there is no whole animal model for the human virus.

I’d like to offer some considerations to your discussion of how to evaluate the relative advantages/disadvantages of latency for the host and virus. Because control of lytic replication by the immune system results in mostly trivial consequences of primary infections, there may have been little selective pressure on the host to either favor or not favor latency. There are serious consequences arising from latency, such as disseminated infection after reactivation in immune-compromised individuals or the virus’s own capacity for immune suppression in the elderly.  But it’s unlikely that these effects on human health would have significant evolutionary implications, because they occur mostly after reproductive capacity wanes. From the virus’s “point of view” (anthropomorphizing), latency and the periodic shedding of virus that is part of the process certainly provides more opportunities for transmission.  So the role of the virus in responding to selection with the development of a latency cycle could have been much more decisive than the role of the host.

HCMV AD169 and Towne, the other strain that has been used a lot in laboratories, were both developed for vaccines. The strategy was attenuation by passage through human fibroblast cell cultures. Again, there was no animal model or cell system. During DNA replication, deletions and rearrangements of the large genome readily occur, and selection for growth in those cultures resulted in viruses with many changes, including as Alan pointed out loss of genes that were non-essential for growth in culture. These strains all failed as vaccines, and a working hypothesis is that they are too attenuated. A strategy for producing better vaccines is to restore at least some of the lost functions (Does that qualify as GOF if it’s still less functional than wild type?). I’m not aware of the current status of those attempts.

Love the podcast, even as the time creeps beyond two hours.


David J. Spector, Ph. D

Professor Emeritus of Microbiology and Immunology

Penn State Hershey

Ross writes:

Hi there TWiVobecs. As always thank you for mutating the latest virology research into enjoyable podcasts. I’ve been listening with interest over the past year or so into the so called “gain of function” controversy. The value of these experiments should seem apparent to anyone with any knowledge of research, let alone virology, so to hear people who should know better making such intellectually dishonest arguments is most disappointing. The name “gain of function” is clearly a case of poisoning the well / weasel words. In all the discussions of what you could call such experiments I’m surprised “modified phenotype” hasn’t cropped up. On pondering the topic it’s the name that seems apt to me. It accurately describes the process without being too wordy or misrepresenting what is happening. In the research that sparked this debate although the virus was more transmissible it was less pathogenic, this is hardly a “gain” more than a modification of phenotype.

I’ve also been enjoying TWiEvo. My honours project was on the change in genetic diversity of arbovirus populations over the course of human infections so I followed the HIV evolution paper with interest.

Regards, Ross

Bill writes:

More CRISPRS to digest

Recent rejoinder to Lander’s article.

Prior items that led to lander’s article and the rejoinder.

critique of above–Disputed/

many more


Alan writes:

I’ve now received my GoViral sampling kit (my pick of a couple of weeks ago), and am officially participating in the program. It turns out they’re enrolling participants in New York, Massachusetts, and California, as those are the only states where they’ve gotten approval for the project. The kit is now sitting here in case I get sick this flu season. However, the odds of that aren’t very high – not only do I rarely get the flu, but this flu season has been quite slow. I just got an email yesterday cancelling the usual biweekly conference call on flu surveillance, because there isn’t enough influenza to justify the discussion.

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