TWiV 349: One ring to vaccinate them all

On episode #349 of the science show This Week in Virology, Vincent, Alan and Rich explain how to make a functional ribosome with tethered subunits, and review the results of a phase III VSV-vectored Ebolavirus vaccine trial in Guinea.

You can find TWiV #349 at

TWiV 346: A double helical career

Episode #346 of the science show This Week in Virology was recorded at the 34th Annual Meeting of the American Society for Virology, where Vincent, Rich, and Kathy spoke with Joan Steitz, a tireless promoter of women in science and one of the greatest scientists of our generation.

You can find TWiV #346 at

TWiV 328: Lariat tricks in 3D

On episode #328 of the science show This Week in Virology, the TWiVocateurs discuss how the RNA polymerase of enteroviruses binds a component of the splicing machinery and inhibits mRNA processing.

You can find TWiV #328 at

TWiV 238: Lost in translation

On episode #238 of the science show This Week in Virology, Vincent, Rich and Kathy discuss mechanisms of protein synthesis and regulation in virus-infected cells.

You can find TWiV #238 at

TWiV 211: Viruses r us

On episode #211 of the science show This Week in Virology, the TWiV four discuss an mRNA-based influenza vaccine, and a phage tubulin that forms a filamentous array in the host cell that is needed for positioning viral DNA.

You can find TWiV #211 at

Aaron J. Shatkin, 77

Aaron J ShatkinAaron J. Shatkin was well known for his work on reoviruses beginning in the 1960s in his laboratory at the Roche Institute of Molecular Biology in Nutley, NJ and then at Rutgers University. He was among the first to appreciate that virus particles contained many different enzymes, such as RNA polymerase and poly(A) polymerase, that could be readily purified and used to study aspects of the viral replication cycle. His studies of reovirus mRNAs revealed an unusual methylated, blocked 5′-terminal structure, m-7G(5′)ppp(5′)G-MpCp-. He found that the 5′-terminal G of reovirus mRNAs made in purified virions or in infected cells was linked to the second G via a 5′-5′ chemical linkage, not the typical 5′-3′ linkage found in nucleic acids. This structure, soon to be called the cap, was subsequently found on many other viral and cellular mRNAs. His laboratory found that the cap is required for efficient translation of mRNA and also for mRNA stability. His discovery of a protein that binds the cap, now called eIF4E, lead to our understanding of how ribosomes are recruited to mRNAs to initiate protein synthesis. In recent years he became interested in the enzymatic machinery in cells that is responsible for synthesis of the cap structure, the capping enzyme. He studied the role of the capping enzyme in the nematode C. elegans and, in one of his last papers, solved the structure of the protein.

I have very good memories of Aaron: in 1979 I interviewed for a postdoctoral position in his laboratory at the Roche Institute (during my seminar I also met Ann Skalka with whom I co-authored a virology textbook many years later). Aaron was the first to offer me a postdoctoral position. I recall him being extremely kind and genuinely interested in my career. When I told him I was also interested in David Baltimore’s laboratory, he quipped ‘You’ll be lucky to even talk to him’; but he had a smile on his face. I was lucky to obtain a position in the Baltimore lab, and when I called Aaron to tell him, he was extremely gracious and congratulatory.

Over the years I met Aaron on many occasions; he was always friendly and cheerful and we often had long scientific conversations. When I moved to Scotch Plains, NJ in 1989 I was surprised to find that Aaron lived just around the corner, less than a mile away. I often saw him jogging by my home on Saturday mornings. Once I pointed him out to my older son: ‘that is the man who discovered the cap on mRNAs!’ My son had just studied the mRNA cap in high school biology so he knew what I meant. After that he often told his friends that the cap-discoverer lived near him in NJ.

Cooper Island rally

Several years ago, when our town wanted to build a home on a nearby small island of land, residents organized a rally to protest the development. It was called ‘Save Cooper Road Island‘ and Aaron and his wife Joan came to lend their support! You can see me with Aaron in photographs of the event (In the photo at left, he is to my left, wearing khaki pants, a dark jacket, and white cap; I am holding a sign, and Joan is to my right).

Just over a year ago he interrupted one of his runs to come by and tell me that his wife had passed away. ‘It’s a bummer’, he said, ‘I have to do all the cooking and cleaning by myself’. I asked him when he was going to retire, and he said now that his wife had died, he would probably keep working as long as he lived. Which he did.

Aaron was a terrific person and scientist. I will miss watching him jog by, telling people that my neighbor discovered the mRNA cap, and thinking about him as I drive past his home. I had planned for years to organize a dinner with him and my Ph.D. mentor, Peter Palese (Peter did a postdoctoral fellowship at the Roche Institute while Aaron was there and knew him well). I also planned to interview Aaron for TWiV. Now I can’t do either. I really should learn not to put off doing important things.


On the Death of Aaron J. Shatkin

Aaron J. Shatkin Ph.D. Obituary

Photos from a presentation (pdf)

TWiV 60: Making viral RNA

TWiV_AA_200Hosts: Vincent Racaniello and Dickson Despommier

Vincent and Dick continue Virology 101 with a discussion of how RNA viruses produce mRNA and replicate their genomes.

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Links for this episode:

Weekly Science Picks
Dick The Double Helix by James D. Watson
Worms and Germs Blog

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Simplifying virus classification: The Baltimore system

baltimore-classificationAlthough many viruses are classified into individual families based on a variety of physical and biological criteria, they may also be placed in groups according to the type of genome in the virion. Over 30 years ago virologist David Baltimore devised an alternative classification scheme that takes into account the nature of the viral nucleic acid.

One of the most significant advances in virology of the past 30 years has been the understanding of how viral genomes are expressed. Cellular genes are encoded in dsDNA, from which mRNAs are produced to direct the synthesis of protein. Francis Crick conceptualized this flow of information as the central dogma of molecular biology:

DNA —> RNA —> protein

All viruses must direct the synthesis of mRNA to produce proteins. No viral genome encodes a complete system for translating proteins; therefore all viral protein synthesis is completely dependent upon the translational machinery of the cell. Baltimore created his virus classification scheme based on the central role of the translational machinery and the importance of viral mRNAs in programming viral protein synthesis. In this scheme, he placed mRNA in the center, and described the pathways to mRNA from DNA or RNA genomes. This arrangement highlights the obligatory relationship between the viral genome and its mRNA.

By convention, mRNA is defined as a positive (+) strand because it is the template for protein synthesis. A strand of DNA of the equivalent sequence is also called the (+) strand. RNA and DNA strands that are complementary to the (+) strand are, of course, called negative (-) strands.

When originally conceived, the Baltimore scheme encompassed six classes of viral genome, as shown in the figure.  Subsequently the gapped DNA genome of hepadnaviruses (e.g. hepatitis B virus) was discovered. The genomes of these viruses comprise the seventh class.  During replication, the gapped DNA genome is filled in to produce perfect duplexes, because host RNA polymerase can only produce mRNA from a fully double-stranded template.

The Baltimore classification system is an elegant molecular algorithm for virologists. The principles embodied in the scheme are extremely useful for understanding information flow of viruses with different genome configurations. When the bewildering array of viruses is classified by this system, we find fewer than 10 pathways to mRNA. By knowing only the nature of the viral genome, the basic steps that must occur to produce mRNA are readily apparent. More pragmatically, the system simplifies understanding the extraordinary life cycle of viruses.

Crick FH (1958). On protein synthesis. Symposia of the Society for Experimental Biology, 12, 138-63 PMID: 13580867

Baltimore D (1971). Expression of animal virus genomes. Bacteriological reviews, 35 (3), 235-41 PMID: 4329869