TWiV 437: Kathy’s new spindle virus

The TWiVsters reveal new giant viruses that argue against a fourth domain of life, and discovery of viruses in the oceanic basement.

You can find TWiV #437 at microbe.tv/twiv, or listen below.

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Forget the fourth domain of life

three domains of lifeWhen giant viruses were discovered – with genomes much larger than any previously seen – some suggested that they had descended from a fourth domain of life (the current three are bacteria, archaea, and eukaryotes). Part of the reason for such a claim was the finding of homologs of bacterial and eukaryotic genes, including molecules involved in translation. Analysis of new giant viruses encoding even more components of the translation machinery has thrown cold water on the fourth domain hypothesis.

Klosneuvirus, with a 1.57 million base pair DNA genome, was discovered in a wastewater treatment plant in Austria, and three related viruses – Indivirus, Hokovirus, and Catovirus – were found in environmental samples.  Sequence analyses suggests that these viruses should be classified in a subfamily of the Mimiviridae.

The Klosneuviruses encode far more components of the translational machinery than do mimiviruses – 25 tRNAs, 19 aminoacyl tRNA synthetases, 11 initiation and elongation proteins, a chain release factor, and tRNA modifying enzymes.

Phylogenomic analyses demonstrate that the aminoacyl tRNA synthetase and translation factor genes are likely derived from protists. This finding is not compatible with the hypothesis that these viruses are derived from a fourth domain of life. It is more likely that smaller ancestors of giant viruses acquired these genes from known eukaryotes.

Why these components of the translational system have been maintained in these giant virus genomes is an excellent question. They might confer some advantage to the viruses, for example when host translation is shut off as a viral defense. Having components of the translational apparatus might allow viral protein synthesis to proceed.

Note that genes encoding ribosomal RNAs or proteins have not been found in any virus. In fact no virus encodes a complete protein synthesis machinery. Maybe they have yet to be discovered? Or perhaps these energetically costly activities are best left to the cell?

 

TWiV 374: Discordance in B

TWiVOn episode #374 of the science show This Week in Virology, the TWiVniks consider the role of a cell enzyme that removes a protein linked to the 5′-end of the picornavirus genome, and the connection between malaria, Epstein-Barr virus, and endemic Burkitt’s lymphoma.

You can find TWiV #374 at microbe.tv/twiv.

TWiV 351: The dengue code

On episode #351 of the science show This Week in Virology, the Masters of the ScienTWIVic Universe discuss a novel poxvirus isolate from an immunosuppressed patient, H1N1 and the gain-of-function debate, and attenuation of dengue virus by recoding the genome.

You can find TWiV #351 at www.microbe.tv/twiv.

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 www.microbe.tv/twiv.

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 www.microbe.tv/twiv.

TWiV 339: Herpes and the sashimi plot

On episode #339 of the science show This Week in Virology, tre TWiV amici present three snippets and a side of sashimi: how herpesvirus inhibits host cell gene expression by disrupting transcription termination.

You can find TWiV #339 at www.microbe.tv/twiv.

TWiV 324: Viruses in the miR may appear more numerous

On episode #324 of the science show This Week in Virology, Lee joins the TWiV team to discuss the value of post-doctoral training, and how a cellular microRNA assists in the replication of hepatitis C virus.

You can find TWiV #324 at www.microbe.tv/twiv.

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 www.microbe.tv/twiv.

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.

Related:

On the Death of Aaron J. Shatkin

Aaron J. Shatkin Ph.D. Obituary

Photos from a presentation (pdf)