TWiV 443: On a leaf, no one can hear you scream

The TWiVsters reveal the puppet master: an RNA virus injected with wasp eggs that paralyzes the ladybug so that she protects the cocoon until the adult emerges.

You can find TWiV #443 at microbe.tv/twiv, or listen below.

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Bodyguard manipulation by a virus

Coccinella septempunctata with Dinocampus coccinellae cocoonHost behavior alteration by viruses is known to assist the development of another organism. An example is a parasitoid wasp that injects viruses along with eggs into a caterpillar. The viral genomes encode proteins that subvert the caterpillar immune response, allowing the wasp larva to develop. A similar strategy may enable safe development of a wasp by a ladybeetle.

The parasitoid wasp D. coccinellae lays its eggs inside a ladybeetle. After 20 days of larval development, a prepupa emerges from the ladybeetle and fabricates a cocoon between the beetle’s legs. At the same time, the ladybeetle becomes paralyzed. It remains on top of the cocoon (pictured; image credit), protecting it until an adult wasp emerges. Remarkably, some ladybeetles then resume their normal lives!

Given what we know about how parasitoid viruses can alter the manipulation of their hosts, it was only logical to search for a virus that paralyzes the ladybeetle. Sequencing of RNA from the heads of parasitized ladybeetles revealed the presence of an RNA virus which the authors call D. coccinellae paralysis virus, DcPV. The virus is a new member of a Iflaviruses, a family of picornavirus-like, (+) strand RNA viruses that infect insects. DcPV was found in wasps in Poland, Japan, and The Netherlands, confirming its cosmopolitain nature.

Viral particles were observed in cells lining the wasp oviducts, but not in the lumen. Viral genomes were undetectable in wasp eggs, became more abundant during hatching, and ceased to replicate in adult wasps. The levels of virus in the ladybeetle abdomen and head increase with time to egress, suggesting that it was transmitted from the wasp larvae to the host. In ladybeetles where the wasp egg did not develop, viral replication does not occur.

DcPV appears to be neurotropic. Before larval egression, no changes were observed in the nervous system of the ladybeetle, but glial cells were full of virus particles. After egression, vaculoles developed in glial cells and neurons degenerated. This damage was less severe in beetles that survived and recovered from paralysis. An expansion of glial cells in these hosts might explain how normal brain functions were restored.

Insects respond to infection with an RNA-based antiviral response. Components of the RNA based immune system were down-regulated during larval development, possibly by viral proteins, allowing virus to invade the nervous system. Resumption of the antiviral reponse might enable recovery of the ladybeetle after emergence of the wasp.

It appears that DcPV is a wasp symbiont that manipulates the behavior of the ladybeetle host to ensure development of wasp offspring. This hypothesis can be tested by removing DcPV from infected wasps, or by adding DCpV to uninfected hosts, and determining the effect on larval development.

We now realize that animals are actually holobionts: an aggregate of eukaryotes, bacteria, and viruses. Therefore host-parasite interactions are really holobiont-holobiont interactions.

TWiV 442: The New York Tim

Freelance science journalist Tim Requarth joins the TWiVers to explain why scientists should stop thinking that explaining science will fix  information illiteracy.

 

You can find TWiV #442 at microbe.tv/twiv, or listen below.

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Twenty-five lectures in virology for 2017

Virology 2017Every year I teach a virology course to undergraduates and masters students at Columbia University. I record video and audio of each of the twenty-five lectures and release them on YouTube – so that not only the students but the rest of the world can learn about the amazing field of virology.

With the spring semester behind us, this year’s lecture series is complete (link to the entire playlist at YouTube). The first 11 lectures cover the fundamentals of virus replication, including virus entry into cells, genome replication, protein synthesis, and assembly. In the remaining 14 lectures we focus on how viruses cause disease, how to prevent or resolve infections, and viral evolution and emergence.

All the lecture slides are also available as pdf files, as well as study questions for each lecture. You can find them at virology.ws/course.

I plan to use these videos to revise my Coursera virology course – which is no longer online – by the end of the summer.

TWiV 441: Don’t ChrY for me influenza

The Beacons of Viral Education (aka the TWiVoners) reveal a cost of being a male mouse – the Y chromosome regulates their susceptibility to influenza virus infection.

You can find TWiV #441 at microbe.tv/twiv, or listen below.

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Flu and the Y chromosome

X and Y chromosomesDisease and death caused by influenza virus are greater in human females than in males. But disease is more common in males from birth through age 15, after which more females are affected. In mice, genetic variation in the Y chromosome controls susceptibility to influenza virus infection (link to paper). Increased susceptibility does not correlate with increased viral replication, but an expanded pathogenic immune response in the lungs.

A panel of mice (strain B6) with the Y chromosome from eleven different strains were used to determine the effect of infection. The mice fell into two groups with distinct high and low survival after intranasal infection with the mouse-adapted PR8 strain of influenza virus. These results show that variation in the Y chromosome influences survival after infection. Furthermore, the previously reported greater susceptibility of female B6 mice to influenza virus infection compared with male mice is due to the presence of the Y chromosome.

Viral replication in the lung does not differ between mouse strains with high and low mortality. Increased mortality is associated with an increase in a type of T lymphocyte called gamma-delta T cells which produce interleukin 17. The latter is known to provoke lung-damaging inflammation.

Differences in susceptibility of mice with different Y chromosomes has nothing to do with the immunosuppressive effects of testosterone. Exactly which genes on the Y chromosome affect influenza virus susceptibility are unknown. Analysis of RNA expression revealed differences in levels of small RNAs in mice of higher versus lower susceptibility. This observation raises the possibility that the Y chromosome might have global effects on gene expression from other chromosomes, which in turn influences susceptibility to infection.

Others have found that the Y chromosome regulates the speed of progression to AIDS in HIV-1 infected men. It seems likely that the Y chromosome has an important general role in modulating the pathogenesis of infectious diseases. A better understanding of how the Y chromosome regulates the expression of other genes will be needed to understand these effects.

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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A different kind of remote control

nucleusAmong the multitudes of eukaryotic viruses with DNA genomes, some replicate in the cell nucleus, while others avoid the nuclear bureaucracy and remain in the cytoplasm. But biology is not always so rigid: a new giant virus has been found that replicates in the cytoplasm, where it seems to recruit components of the nuclear transcription machinery (link to paper).

Noumeavirus was isolated from a pond near – where else? – Noumea airport in New Caledonia. The 200 nanometer icosahedral particles infect the amoeba Acanthamoeba castellani and have a double-stranded DNA genome of 376,207 base pairs encoding 452 proteins. Sequence comparisons revealed Noumeavirus to be a new member of the family Marseilleviridae, which  includes other previously discovered giant viruses.

Other members of the Marseilleviridae replicate in the cytoplasm of the host cell, so it was assumed that the related Noumeavirus would do the same. However an analysis of the proteins in purified virus particles revealed an absence of components of the transcriptional machinery – which is needed for ths synthesis of mRNA. RNA polymerase, for example, is readily detected in other cytoplasmic viruses such as Mimivirus and poxviruses.

If proteins involved in transcription are not present in the Noumeavirus particle, and the virus does not enter the nucleus, how are viral mRNAs produced?  It appears that early in infection, the required proteins are moved from the nucleus to sites of viral replication in the cytoplasm. When nuclear proteins were labled with green fluorescent protein, within one hour after infection they can be seen moving out of the nucleus into the cytoplasm to sites of viral replication. The nuclear integrity remains intact, as host DNA does not leave the organelle. This recruitment of nuclear proteins is transient:  after 2-4 hours proteins are no longer leaving the nucleus.

This series of events suggests that nuclear proteins needed to initiate viral mRNA synthesis are recruited from the nucleus to sites of viral replication in the cytoplasm. Once viral mRNAs are made, the viral transcriptional machinery can be assembled and the nuclear proteins are no longer needed. The authors call this ‘remote control of the host nucleus.’

Confirmation of this hypothesis will require the demonstration that nuclear proteins involved in viral mRNA synthesis are recruited to early sites of viral replication in the cytoplasm. It will also be essential to identify the mechanism by which these nuclear proteins are extracted. Perhaps one or more virion proteins, such as an abundant 150 amino acid protein of unknown function, is involved.

Other giant viruses, such as Mimivirus, package the viral transcriptional machinery in the virus particle and are independent of the cell nucleus. At the other extreme are viruses that undergo transcription and DNA synthesis entirely in the nucleus (e.g., herpesviruses). Perhaps Noumeavirus is a relic of an evolutionary transition between the two replication strategies.

Image credit

TWiV 439: The purloined envelope

Paul Bieniasz joins the TWiV team to talk about the co-option, millions of years ago, of an endogenous retrovirus envelope protein by hominid ancestors for host defense against viral infection.

 

You can find TWiV #439 at microbe.tv/twiv, or listen. below.

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TWiV 438: Drs. TWiV go to Washington

On the eve of the March for Science, the TWiV team gathers at ASM Headquarters in Washington, DC with guests Stefano and Susie to talk about the state of science communication.

You can find TWiV #438 at microbe.tv/twiv, or watch above/listen below.

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