TWiV 483: Every infection is unhappy in its own way

Vincent and the Virals review undermining of antiviral effectiveness by genital inflammation, and heterogeneity of influenza virus infection in single cells.

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Influenza virus in the eye

By Gertrud U. Rey

Gertrud Rey is a trained virologist residing in Atlanta, Georgia. During the day, she works as a consultant in a biotech patent law firm, but spends much of her free time as a science communicator. She was a guest on TWiV 179 and 424.

Although the dominant mode of transmission for influenza virus is via the respiratory route, there is growing evidence to suggest that various human and avian influenza viruses are capable of entering the body following ocular exposure.

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How a toupee compromised influenza vaccine

The influenza virus vaccine is frequently updated to ensure that it protects against infection with circulating virus strains. In some years the vaccine matches the circulating strains, but in others, there is a mismatch. The result is that the vaccine is less effective at protecting from infection. During the 2014-15 influenza season there was a mismatch due to growing the vaccine in embryonated chicken eggs.

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TWiV 467: Jon and Ted’s Excellent Adventure

Jon and Teddy Yewdell join the TWiV team to talk about their careers, their research, and the problems with biomedical research.

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TWiV 460: Penn, a great sandbox for science

Vincent travels to the University of Pennsylvania and speaks with virologists Gary Cohen, Scott Hensley, Carolina Lopez, and Susan Weiss about their careers and their research.

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TWiV 457: The Red Queen meets the White Rabbit

Brianne returns to the TWiV Gang to discuss the distribution of proteins on the influenza viral genome, and the evolution of myxoma virus that was released in Australia to control the rabbit population.

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TWiV 452: Kiss that frog

Lynda Coughlan joins the weekly virtual bus companions for a discussion of a host defense peptide from frogs that destroys influenza virus, and mouse models for acute and chronic hepacivirus infection.

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Kermit’s urumi

Hydrophylax bahuvistaraFrogs don’t get flu (as far as I know) but their skin contains a peptide that inhibits the replication of influenza virus (link to paper).

Frog skin contains host defense peptides (HDPs), part of the innate immune defenses of many species. They were first found in amphibians by Michael Zasloff, who, as part of his research, performed surgery on frogs and then returned them to an aquarium – which was not sterile. He wondered why the frogs always healed without signs of infection, which lead him to discover the antimicrobial peptides, called magainins, in frog skin. HDPs had been first discovered years earlier in the silk moth.

Amphibian HDPs are active against bacteria, fungi, viruses, and protozoa. To discover HDPs that inhibit influenza virus, 32 HDPs from skin secretions of the Indian frog Hydrophylax bahuvistara were screened by mixing them with virus followed by a plaque assay. One peptide was found to potently inhibit influenza virus replication without cell toxicity. It was called urumin, after the whip sword known as urumi.

Urumin inhibits infectivity of influenza H1N1 viruses far better than H3N2 viruses. The reason is that the peptide targets the viral H1 hemagglutinin, one of two glycoproteins in the viral envelope. Furthermore, the peptide appears to interact with the conserved stalk region of the HA glycoprotein, and not with the globular head.

Currently two different antiviral drugs, oseltamivir and relenza, are used to control influenza virus infection. Viruses resistant to these drugs were still inhibited by urumin, indicating that should urumin ever be licensed, it would be useful in the event that oseltamivir and relenza resistant viruses became more common.

Examination of urumin treated virus particles by electron microscopy revealed that they are disrupted by the peptide. How urumin breaks influenza virus particles is not known. However, the HDP nisin destroys bacteria by first binding to a bacterial membrane component, then moving into the membrane. After binding to HA, urumin might in a simlar way disrupt the membrane of influenza virus particles.

Urumin also reduced disease, death, and the amount of virus in the lung in mice intranasally infected with influenza virus.

These observations suggest that urumin is worthy of additional study as an influenza virus inhibitor. HDPs are attractive antimicrobial compounds because resistance to their mechanisms of action is lower than for other types of inhibitors. However, enthusiasm for urumin is dampened because, despite extensive study, no HDP has yet been approved by the US Food and Drug Administration for use in humans. The obstacles to therapeutic success of HDPs have not been identified.

TWiV 446: Old sins die hard

The TWiV hosts review an analysis of gender parity trends at virology conferences, and the origin and unusual pathogenesis of the 1918 pandemic H1N1 influenza virus.

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TWiV 436: Virology above Cayuga’s waters

At Cornell University in Ithaca, New York, Vincent speaks with Susan, Colin, and Gary about the work of their laboratories on parvoviruses, influenza viruses, and coronaviruses that infect dogs, cats, horses and other mammals.

You can find TWiV #436 at microbe.tv/twiv, or listen below.

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