TWiV 150: Contaminated

pXMRVHosts: Vincent RacanielloRich Condit, and Dickson Despommier

Vincent, Dickson, and Rich meant to do an all-email episode, but first they review results of the Blood XMRV Scientific Research Working Group, and partial retraction of the paper associating XMRV with chronic fatigue syndrome.

With this episode TWiV is three years old.

Click the arrow above to play, or right-click to download TWiV 150 (56 MB .mp3, 93 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Dickson – The Tree of Life
Vincent –
When do you fact-check article content with sources? (take as directed)
Rich –
io9

Listener Pick of the Week

LuisNIH videocasting and podcasting

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 82: Immunology in silico

Hosts: Vincent Racaniello and Rich Condit

On episode #82 of the podcast This Week in Virology (TWiV), Vincent and Rich talk about how thymic selection of T cells might lead to better control of HIV-1 infection, and a mouse model for severe antibody-induced dengue virus disease.

This episode is sponsored by Data Robotics Inc. Use the promotion code TWIVPOD to receive $75-$500 off a Drobo.

Win a free Drobo S! Contest rules here.

Click the arrow above to play, or right-click to download TWiV #82 (59 MB .mp3, 82 minutes)

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Links for this episode:

Weekly Science Picks

Rich The Mold in Dr. Florey’s Coat: The Story of the Penicillin Miracle by Eric Lax
Vincent Proteopedia (thanks, Erik!)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Immunopathology: Too much of a good thing

influenzaIn many viral infections, clinical symptoms such as fever, tissue damage, pain, and nausea are a consequence of the immune response. Damage caused by the immune system  is known as immunopathology. For some viruses that do not directly kill cells (non-cytolytic viruses) the immune response is the main cause of disease. Immunopathology may be caused by antibodies, an excessive innate response, or lymphocytes. Consequently, it has been proposed that the symptoms of a virus infection could be ameliorated by inhibiting the immune response. A paper in the 21 January online issue of PNAS demonstrates that immune modulation with a sphingosine analog significantly dampens the cytokine response in mice infected with influenza virus, thereby reducing tissue injury.

The authors used intranasal infection of mice with the WSN strain of influenza virus that had been modified to produce CD8 and CD4 T cell receptor epitopes from another virus, lymphocytic choriomeningitis virus. The inclusion of these sequences allowed the authors to measure virus-specific T cells in the infected animals. The effect of the sphinogosine analog AAL-R was then determined. This compound was selected because it had been shown previously to reduce virus-specific T cell accumulation in the lung. When administered in the respiratory tract, AAL-R reduced the anti-influenza virus T cell response and the release of cytokines and chemokines. Infiltration of macrophages and polymorphonuclear leukocytes into the lung was inhibited, and lung injury decreased. However, the drug did not increase the replication of virus in the lungs, and anti-viral antibody levels were unaffected. These effects were observed even when AAL-R was given 4 days after virus infection. Finally, the authors show that the drug acts by reducing the levels of major histocompatibility class I and II molecules, and the co-stimulatory B7-2 molecule, from dendritic cells in the lung and draining lymph nodes. The result is a reduction in the number of virus-specific T cells in the lung.

The studies reported here provide a better understanding of influenza virus induced injury of the lung. It may also be possible to use sphingosine analogs to decrease lung injury in human influenza infections, a possibility that the authors are exploring. Such compounds might be especially effective when used together with antiviral drugs such as Tamiflu and Relenza. This combination therapy approach would have the dual benefit of reducing viral loads and suppressing lung damage.

D. Marsolais, B. Hahm, K. B. Walsh, K. H. Edelmann, D. McGavern, Y. Hatta, Y. Kawaoka, H. Rosen, M. B. A. Oldstone (2009). A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infection Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0812689106