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 458: Saliva of the fittest

The TWiVians present an imported case of yellow fever in New York City, and explain how a dengue virus subgenomic RNA disrupts immunity in mosquito salivary glands to increase virus replication.

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TWiV 456: Be careful of canons

Brianne joins the TWiVMasters to explain how mutations in genes encoding RNA polymerase III predispose children to severe varicella, and detection of an RNA virus by a DNA sensor.

 

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Phage synergy with the immune system

bacteriophage modelNot long after their discovery, viruses that infect bacteria – bacteriophages – were considered as therapeutic agents for treating infections. Despite many years of research on so-called phage therapy, clinical trials have produced conflicting results. They might be explained in part by the results of a new study which show that the host innate immune system is crucial for the efficacy of phage therapy.

When mice are infected intranasally with Pseudomonas aeruginosa (which causes pneumonia in patients with weak immune systems), the bacterium multiplies in the lungs and kills the animals in less than two days. When a P. aeruginosa lytic phage (i.e. that kills the bacteria) is instilled in the nose of the mice two hours after bacterial infection, all the mice survive and there are no detectable bacteria in the lungs. The phage can even be used prophylactically: it can prevent pneumonia when given up to four days before bacterial challenge.

The ability of phage to clear P. aeruginosa infection in the mouse lungs depends on the innate immune response. When bacteria infect a host, they are rapidly detected by pattern recognition receptors such as toll-like receptors. These receptors detect pathogen-specific molecular patterns and initiate a signaling cascade that leads to the production of cytokines, which may stop the infection. Phage cannot clear P. aeruginosa infection in mice lacking the myd88 gene, which is central to the activity of toll like receptors. This result shows that the innate immune response is crucial for the ability of phages to clear bacterial infections. In contrast, neither T cells, B cells, or innate lymphoid cells such as NK cells are needed for phage therapy to work.

The neutrophil is a cell of the immune system that is important in curtailing bacterial infections. Phage therapy does not work in mice depleted of neutrophils. This result suggests that humans with neutropenia, or low neutrophil counts, might not respond well to phage therapy.

A concern with phage therapy is that bacterial mutants resistant to infection might arise, leading to treatment failure. In silico modeling indicated that phage-resistant bacteria are eliminated by the innate immune response. In contrast, phage resistant bacteria dominate the population in mice lacking the myd88 gene.

These results demonstrate that in mice, successful phage therapy depends on a both the innate immune response of the host, which the authors call ‘immunophage synergy’. Whether such synergy also occurs in humans is not known, but should be studied. Even if observed in humans, immunophage synergy might not be a feature of infections in other anatomical locations, or those caused by other bacteria. Nevertheless, should immunophage synergy occur in people, then clearly only those with appropriate host immunity – which needs to be defined – should be given phage therapy.

TWiV 449: The sound of non-silencing

The TWiV Council explores the finding that facial appearance affects science communication, and evidence that RNA interference confers antiviral immunity in mammalian cells.

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TWiV 426: I’m Axl, and I’ll be your cervid today

The sages of TWiV explain how chronic wasting disease of cervids could be caused by spontaneous misfolding of prion protein, and the role of the membrane protein Axl in Zika virus entry into cells.

You can find TWiV #426 at microbe.tv/twiv, or listen below.

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TWiV 392: Zika virus!

Four virologists discuss our current understanding of Zika virus biology, pathogenesis, transmission, and prevention, in this special live episode recorded at the American Society for Microbiology in Washington, DC.

You can find TWiV #392 at microbe.tv/twiv, or listen/watch below.

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TWiV 359: A Blossom by any other name

On episode #359 of the science show This Week in Virology, Vincent speaks with Blossom about her laboratory’s research on Kaposi’s sarcoma-associated herpesvirus, including how it transforms cells, the switch between lytic and latent replication, and its interaction with the innate immune system of the host.

You can find TWiV #359 at www.microbe.tv/twiv.

TWiV 358: Virology and proteomics with Ileana Cristea

On episode #358 of the science show This Week in Virology, Vincent meets up with Ileana at Princeton University to talk about how her laboratory integrates molecular virology, mass spectrometry-based proteomics, and bioinformatics to unravel the interplay between virus and host.

You can find TWiV #358 at www.microbe.tv/twiv.

TWiV 353: STING and the antiviral police

On episode #353 of the science show This Week in Virology, the TWiVniacs discuss twenty-eight years of poliovirus shedding by an immunodeficient patient, and packaging of the innate cytoplasmic signaling molecule cyclic GMP-AMP in virus particles.

You can find TWiV #353 at www.microbe.tv/twiv.