TWiV 440: I hardly noumeavirus

No problem not being nice to Dickson in this episode, because he’s absent for a discussion of a new giant virus that replicates in the cytoplasm yet transiently accesses the nucleus to bootstrap infection.

You can find TWiV #440 at microbe.tv/twiv, or listen below.

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TWiV 433: Poops viruses and worms

The lovely TWiV team explore evolution of our fecal virome, and the antiviral RNA interference response in the nematode C. elegans.

You can find TWiV #433 at microbe.tv/twiv, or listen below.

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TWiV 432: Conjunction junction, what’s your function?

The TWiVites discuss Zika virus seroprevalence in wild monkeys, Zika virus mRNA vaccines, and a gamete fusion protein inherited from viruses.

You can find TWiV #432 at microbe.tv/twiv, or listen below.

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TWiV 424: FLERVergnügen

Trudy joins the the TWiVlords to discuss new tests for detecting prions in the blood, and evidence showing that foamy retroviruses originated in the seas with their jawed vertebrate hosts at least 450 million years ago.

You can find TWiV #424 at microbe.tv/twiv, or listen below.

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Interview with Harmit Malik

Vincent Racaniello interviews Harmit Malik, PhD, Fred Hutchinson Cancer Research Center. Harmit and his laboratory are interested in a variety of problems that are characterized by evolutionary conflict.

This video is one of 26 video interviews with eminent virologists that are part of the supplemental material for Principles of Virology, 4th Edition, published by ASM Press. Other interviews in this series can be found at this link.

TWiV 422: Watching the icosahedron drop

The TWiVestigators wrap up 2016 with a discussion of the year’s ten compelling virology stories.

You can find TWiV #422 at microbe.tv/twiv, or listen below.

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MicrobeTV

MicrobeTVI started my first podcast, This Week in Virology, in September 2008, together with Dickson Despommier, father of the Vertical Farm. Although I viewed the creation of a science podcast as an experiment, I was surprised when people began to listen. Since then I have created five other podcasts, scattered at different websites. Now you can find all of them at MicrobeTV.

MicrobeTV is a podcast network for people who are interested in the life sciences. More specifically, the podcasts of MicrobeTV use conversations among scientists as teaching tools. Although I have been a research scientist my entire career, I have also had opportunities to teach graduate students, medical students, and undergraduate students. A long time ago I realized that I love to teach, and my podcasts are the outside-the-classroom expression of that sentiment.

My original idea behind TWiV was to teach virology to the broader public by recording conversations among scientists. The success of this approach led me to create This Week in Parasitism, This Week in Microbiology, Urban Agriculture, and This Week in Evolution, all of which can now be found at MicrobeTV.

You may ask why I do so many podcasts. The answer is simple – because I love talking about science and teaching others about this amazing field that makes our lives better. I could not do all these podcasts without my terrific co-hosts. I am also grateful to the American Society for Microbiology for their assistance and support for many years, especially Chris Condayan and Ray Ortega and the Communications Department.

MicrobeTV is the home for all of the podcasts that I have produced (and there are more to come!). But I’d also like to use MicrobeTV as a platform to showcase other science shows. The requirements are few: you should be passionate about your subject, you should have a great relationship with your audience, and your podcast audio must be excellent. If you are interested in joining MicrobeTV, send a note to shows@microbe.tv.

MicrobeTV – Science Shows by Scientists.

TWiEVO: This Week in Evolution

TWiEVOTo a molecular biologist, the word ‘evolution’ evokes images of fossils, dusty rocks, and phylogenetic trees covering eons. The fields of molecular biology and evolutionary biology diverged during the twentieth century, but new experimental technologies have lead to a fusion of the two disciplines. The result is that evolutionary biologists have the unprecedented ability to evaluate how genetic change produces novel phenotypes that allow adaptation. It’s a great time to start a new podcast on evolution!

Molecular biology is an experimental approach that was born in 1953 with the discovery of the structure of DNA. Its goal is to understand how cells and organisms work at the level of biological molecules such as DNA, RNA, and proteins. Some of the experimental tools of molecular biology include recombinant DNA, nucleotide sequencing, mutagenesis, and DNA-mediated transformation. The experiments of molecular biology often involve simplified, or reductionist systems in which much of the complexity of nature is ignored. Variation in individuals, populations, and the environment are set aside. Data produced by the techniques of molecular biology can lead to decisive conclusions about cause and effect.

Evolutionary biology embraces variation, and in fact attempts to explain it. The basis for variation in organisms is usually inferred by associating phenotypes, sequences, and alleles. The problem with this approach is that alternative explanations are often plausible, and conclusions are rarely as decisive as those achieved with molecular biology. We can turn to Darwin’s finches as a good illustration of the difference between fields. Darwin hypothesized that variation in the beaks of finches was a consequence of diet, but how such variation occurred was unknown. It was not until 2004 that it was shown that beak shape and size could be controlled by two different genes.

The techniques of DNA sequencing, mutagenesis, and the ability to introduce altered DNA into cells and organisms have been the catalyst for the fusion of molecular biology and evolutionary biology into a new and far more powerful science, which Dean and Thornton call a ‘functional synthesis’. As a consequence, genotype can be definitively connected with phenotype, allowing resolution of fundamental questions in evolution that have been puzzles for many years.

Microbes are perfect subjects for study by evolutionary biologists, as they are readily manipulable and rapidly reproduce. However no organism is now very far from the eye of this new science. Subjects as diverse as insecticide resistance, coat color in mice, evolution of color vision, and much more are all amenable to scrutiny by the ‘functional synthesis’.

This Week in Evolution will cover all aspects of the functional synthesis, irrespective of organism. My co-host is Nels Elde, an evolutionary biologist at the University of Utah. Nels has appeared on This Week in Virology to discuss the evolution of virus-host conflict, and his lab’s story on the evolutionary battle for iron between mammalian transferrin and bacterial transferrin-binding protein was covered on This Week in Microbiology.

You can find This Week in Evolution at iTunes and at MicrobeTV.

TWiV 367: Two sides to a Coyne

On episode #367 of the science show This Week in Virology, two Coynes join the TWiV overlords to explain their three-dimensional cell culture model of polarized intestinal for studying enterovirus infection.

You can find TWiV #367 at www.microbe.tv/twiv.

Exaptation: A cell enzyme becomes a viral capsid protein

Alphalipothrixvirus virionThe acquisition of a capsid is thought to be a key event in the evolution of viruses from the self-replicating genetic elements that existed during the pre-cellular stage on Earth. The origin of viral capsids has been obscure because their components are not similar to cellular proteins. The discovery that a viral capsid protein evolved from a CRISPR-associated nuclease provides insight into how viruses emerged.

Thermoproteus tenax virus 1 (TTV1) infects the hyperthemophilic archaeon Thermoproteus tenax, which grows at 86°C. The enveloped virus particles are flexible filaments 400 nm long and 40 nm in diameter (illustrated; image credit) built with four capsid proteins, TP1-TP4. The basic proteins TP1 and TP2 bind the 16 kb double-stranded DNA genome to form the nucleocapsid.

Thirty years after the discovery of TTV1, the capsid proteins remained ORFans – meaning that they had no sequence homology with viral or cellular proteins. Recently a more sensitive homology analysis revealed that TP1 is similar to Cas4, a nuclease that is a part of the prokaryotic CRISPR-Cas defense system.

Although TP1 clearly matches the Cas4 protein, it is not complete: codons at the carboxy-terminus are missing. A re-examination of the TTV1 genome sequence revealed a previously undetected open reading frame of 74 codons just downstream of the TP1 gene which are the missing C-terminal residues of the Cas4 nuclease. It is not known if this protein, called gp7, is produced in infected cells; it is not part of the virus particle.

Together the TP1 and gp7 proteins represent a full length Cas4 nuclease. TP1 is probably not catalytically active due to amino acid changes in the active site of the enzyme.

Why does TP1 lack the carboxy-terminal residues of Cas4? The amino terminus of the TP1 protein comprises a positively charged surface that might be involved in binding the viral DNA genome. The same surface in Cas4 is covered by the carboxy-terminal domain of the protein. This observation suggests that transformation of Cas4 from a nuclease into a viral capsid protein probably required removal of this shielding domain, so that the protein could bind the DNA genome.

How did a nuclease become a viral capsid protein? An ancestor of TTV1 might have encoded a Cas4-like protein with nuclease activity with a role in genome replication or repair. Mutations causing loss of nuclease activity might have been followed by truncation of the protein to expose the DNA binding domain, which then became a viral capsid protein. Support for this idea comes from the observation that a Cas4-like protein encoded in the genome of another archaeal virus, the rudivirus SIRV2, has nuclease activity.

Exaptation, a change in the function of a protein during evolution, is known to have taken place in the viral world. The case of Cas4 and TP1 shows that capsid components can evolve from proteins with a very different function.