TWiV 338 letters

Benji writes:

Dear Vincent and friends

I’m a third year medical student at University College London doing some research in oncolytic measles virus and enjoy listening to your show regularly.

I couldn’t help but pick up on the question from yesterday about why IRF7 deficiency should cause leukemia and what on earth interferon has to do with anti-cancer immune surveillance.

Well from my field I can confirm that a whole series of studies, cited below, have shown defective type I IFN responses in cancer cells such as ovarian cancer cells.

But why would a cancer cell activate interferon pathway in the first place?

Well I haven’t been able to find an explanation in the literature, but I have a “hypochondriac cancer theory” that I’d love to share with you. During the rapid cell cycling of a cancer cell, they may well have lots of cytoplasmic DNA and RNA floating around while they rapidly dive in and out of mitosis.

But DNA and RNA floating around in the cytoplasm looks like something else to the cell: a virus!

So some cancer cells could be getting tricked into thinking they are virally infected and start producing lots of interferon, stop translation, and activate NK and T-cells nearby. Some successful cancers though will have a defective or inhibited a component or two of the IFN pathway and survive.

So this could be a tidy explanation as to why patients like patient P with defective IRF genes are more likely to develop leukaemia. Their cells are just as hypochondriac as everyone else’s, but they don’t have the phone number (interferons) to call the doctor.

What do you guys think?

I’ve made an assumption or two along the way, but I can’t for the life of me think of how to prove that there’s RNA and DNA hanging out in the cytoplasm of cancer cells, do you have any advice for how to measure that?
Best wishes
MBBS Yr3, Immunology, Infection & Cell Pathology IBSc

Krishnamurthy, S, Takimoto, T, Scroggs, RA and Portner, A (2006). Differentially
regulated interferon response determines the outcome of Newcastle disease virus
infection in normal and tumor cell lines. J Virol 80: 5145–5155.

Obuchi, M, Fernandez, M and Barber, GN (2003). Development of recombinant
vesicular stomatitis viruses that exploit defects in host defense to augment specific
oncolytic activity. J Virol 77: 8843–8856.

HARALAMBIEVA, I., IANKOV, I., HASEGAWA, K., HARVEY, M., RUSSELL, S. J. & PENG, K. W. 2007. Engineering oncolytic measles virus to circumvent the intracellular innate immune response. Mol Ther, 15, 588-97.

Timothy writes:

Dear TWIV Family,

Thank you again for showcasing my work on Episode 273 “Lambda is not just a phage.” A non-virologist crystallographer friend of mine at Rockefeller sent me a note after that aired saying that “you know you’ve made it when you are on TWIV.” It’s really an honor and yet more confirmation that the breadth of your audience is wide.

I’ve been experimenting with new ways for me to share scientific information. Since the previous version of that LCM movie I’d made didn’t have a voice over or much context, I decided to embed the LCM video within a “video abstract. ” I talk about the techniques we used in our Cell Host and Microbe paper and talk about results and context in broad strokes. See the link below. I hope you enjoy it! I hope that this movie and future movies will help increase public engagement in virology. Keep up the good work!


Richard writes:

Dear Twixonauts
I am a registered nurse in Illinois, and very much appreciate your podcasts. I ran across an fictional application of parasitism in a science fiction novel entitled Blind Lake, by Robert Charles Wilson. It’s not a spoiler to describe it on your episode, as the particular biological mechanism in question does not relate directly to the plot. The novel describes an alien species with a technological civilization that is diurnal, working by day and sleeping at night. Every night, small creatures enter the home to suckle a body fluid secreted by small nipples for the purpose. When an individual adult dies, or becomes disabled due to injury, illness, or old age, the desire for a replacement causes the members of its group to activate an endogenous virus. The virus infects the parasites, some of which then begin a process of maturation, culminating in the development of adult aliens.

The author does not elaborate further, but it occurs to me that this reproductive modality allows for mechanisms for genetic recombination distinctly different from that seen in sexual reproduction. Individual parasites might be coinfected by viruses produced by more than one adult, so if the virus is segmented, like influenza, the virus might recombine. Furthermore, if there were transmission between individuals at the parasitic stage, the virus could carry genes from one adult to another.

For those listeners who prefer to skip to this description, it may be found on the seventh page of chapter 33, though I imagine that the author would prefer that one purchase and read the entirety of his book.

Here in the Chicago area it is a sunny 50 degrees F (10 C), wind 8 mph, dew point 26. The neutrino flux is 65 billion particles per square cm per second.

Erika writes:

To the fabulous TWIV Team,

I wanted to say thank you for making this amazing podcast! I found TWIV a little over a year ago while looking through iTunes and it has been a fantastic weekly addition to my life ever since.

I graduated in 2014 from the University of Florida with my bachelors in microbiology and cell science and am currently working as a laboratory technician at the university. I knew I wanted to work in virology before TWIV, but this podcast has helped solidify and intensify my dream of becoming a virologist!

After listening to the podcasts and perusing the website, I have begun thinking about doing science communication work in the future. I want to work to communicate topics in science in a simple way to the general public to attempt to branch the gap in science literacy. I don’t think I would have ever realized this passion without the ideas from TWIV!

My biggest thank you is for the advertisement for the Icahn School of Medicine at Mount Sinai’s PhD program. I applied after listening to the advertisement on TWIV and interviewed this January. I fell in love with the program, faculty, and, of course, New York City. I am beginning my PhD with them in August and I don’t think I would have ended up with this amazing opportunity without TWIV.

I recommend this podcast to everyone I know, whether they have a science background or not. I just want to say THANK YOU for the long-lasting impact you’ve made on my life and keep up the amazing work!

​P.S. We are having beautiful weather here in Gainesville! It’s 80°F/27°C, partly cloudy with 59% humidity and winds at 9mph/14kmh.​

May writes:

Dear Vincent and the TWiV masters,

Love the Show!

I came to TWiV via Vincent’s Virology course on YouTube. Since I’m a sales rep for a biotech company, I have tons of windshield time (think of driving from Johns Hopkins to Virginia Tech), I sustain on audio books and podcasts. Ever since I discovered TWiV, the only voice in my car is from you guys. I love the show so much that I downloaded the Microbe World App so that I can start from Episode #1, today I just finished Episode #100 when you interviewed David Baltimore. He was at Johns Hopkins a month ago. I could not make it to his seminar. I wish I could. Bought the book (Ahead of the Curve: David Baltimore’s Life in Science) you recommended on Amazon.

I learned a lot from the show. For example, I learned from TWiV that CMV is the only virus that can cross the placenta. I think I sort of know. Sadly a friend of mine had CMV when she was pregnant and her baby girl had lots of problems from the infection. But nobody told me point blank, “CMV is the only virus that can cross the placenta”. TWiV clarify or solidify that idea for me.

So I walked into a lab today (before listening to the David Baltimore episode) to follow up on a project. It’s a CMV lab, so I asked the PI, “Have you or anybody in the field figured out why CMV is the only virus that can cross the placenta? What makes this virus so unique?” He said, “That is what this project is about. We want to tag the virus with a reporter, then mutate different genes and see which one makes difference.” Wow, I just have a new level of understanding of what he’s doing.

This is not the only example. I’m embarrassed to admit that it’s from TWiV that I learned RNAi does not quite work in mammalian cells. I don’t know how I missed that. I used to call on Tom Tuschl and Andy Fire. I read Genetic Engineering News, Nature Method, etc. Hgh?

I’m also glad to hear that LIPS (luciferase immunoprecipitation system) is catching on. I remember talking to Peter Burbelo (who developed the method) ten years ago, and I was skeptical. I think the CDC person mentioned the assay in the episode about MRES virus. I know a lab at Virgina Tech adopted the assay. It’s more sensitive. More labs should try it.

Just want to say thank you for the great show you produce. Keep up the good work, and please please do not stop producing the show. I’m addicted to it.

The weather here is hot and muggy. 27C, 52% humidity. It’s a pre-show of August.


Rockville, MD

Peter writes:

Greetings Vincent, Dickson, Alan, Rich and Cathy

I have a couple of listener picks of the week:
Swedish statistician Hans Rosling discussing how West Africa has managed to contain the Ebola virus:

There is more from Hans Rosling at A Swedish Non-Profit organisation which promotes a fact based world view.

Some more podcasts that may be of interest.
On a recent TWiM you mentioned the journal eLife, browsing their site I see that they have a podcast:
The eLife Podcast is produced for eLife by Dr Chris Smith and the Cambridge University team that also produce the The Naked Scientists Podcast


Will Professor Racaniello be running any more virology courses on Coursera this year?