Research: How Flu Succeeds

 

 

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Perhaps the biggest `up side’ to this, or any pandemic, is the increase in research into the science of virology and influenza viruses.   After decades of neglect, influenza is suddenly a `hot’ topic for investigation.

 

Vaccine technologies, new antivirals, even NPI’s (Non Pharmaceutical Interventions) are getting closer scrutiny.   While many of these advances won’t do much for us with this pandemic virus, they hold promise for the next pandemic . . . or the one after that.

 

As incredible as it sounds, there is still much we don’t know about how influenza works in the body, how it is spread, or why some people get very ill while others can be infected without symptoms.

 

But there are research centers around the world working to answer these, and other questions.   

 

Today we get a fascinating look at some of the research being conducted by the Burnham Institute of Medical Research, Mount Sinai School of Medicine ,the Salk Institute for Biological Studies and the Genomics Institute of the Novartis Research Foundation (GNF) who have identified 295 Host factors that help flu throughout its lifecycle.

 

Below you’ll find excerpts from the Burnham press release.  There is also a short (2 minute) video on the website explaining about some of this research.

 

The full findings are published the Journal Nature, and I’ve provided a link and an excerpt from the abstract, as well.

 

 

 

How Flu Succeeds

Investigators identify host factors that help multiple influenza strains thrive and could be targeted for new antivirals

LA JOLLA, Calif., December 21, 2009 -- Investigators at Burnham Institute for Medical Research (Burnham), Mount Sinai School of Medicine (Mount Sinai), the Salk Institute for Biological Studies (Salk) and the Genomics Institute of the Novartis Research Foundation (GNF) have identified 295 human cell factors that influenza A strains must harness to infect a cell, including the currently circulating swine-origin H1N1. The team also identified small molecule compounds that act on several of these factors and inhibit viral replication, pointing to new ways to treat flu. These findings were published online on December 21 in the journal Nature.

 

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Influenza A virus contains only enough genetic information (RNA) to produce 11 proteins and must co-opt host cellular machinery to complete its life cycle. Sumit Chanda, Ph.D., of Burnham, Megan Shaw, Ph.D., of Mount Sinai, John Young, Ph.D., of Salk, Yingyao Zhou, Ph.D., of GNF and others used RNAi screening technology to selectively turn off more than 19,000 human genes to determine which human factors facilitate viral entry, uncoating, nuclear import, viral replication and other necessary functions of the virus.

 

“Because influenza mutates so readily, it has become a moving target for therapeutic intervention, making it difficult to treat circulating strains, including the H1N1 swine flu,” said Dr. Chanda. “As a result, there is now widespread resistance to two classes of antiviral drugs. However, by targeting more stable human host factors, we may be able to develop therapies that prevent or treat a variety of influenza A strains and are more likely to maintain their effectiveness.”

 

“This study has provided us with crucial knowledge of the cellular pathways and factors the influenza virus exploits to replicate” added Dr. Shaw. “Each of these represents an ‘Achilles heel’ of the virus and vastly increases the number of potential targets for new influenza antiviral drugs.”

(Continue . . . )

 

 

The Nature journal article. doi:10.1038/nature08699

 

Human host factors required for influenza virus replication near-final version

Renate König1,9, Silke Stertz4,9, Yingyao Zhou7, Atsushi Inoue1, H. -Heinrich Hoffmann4, Suchita Bhattacharyya2, Judith G. Alamares4, Donna M. Tscherne4, Mila B. Ortigoza4, Yuhong Liang4, Qinshan Gao4, Shane E. Andrews3, Sourav Bandyopadhyay8, Paul De Jesus1, Buu P. Tu7, Lars Pache1, Crystal Shih1, Anthony Orth7, Ghislain Bonamy7, Loren Miraglia7, Trey Ideker8, Adolfo García-Sastre4,5,6, John A. T. Young2, Peter Palese4,5, Megan L. Shaw4,9 & Sumit K. Chanda1,9

 

 

Influenza A virus is an RNA virus that encodes up to 11 proteins and this small coding capacity demands that the virus use the host cellular machinery for many aspects of its life cycle1.

 

 

Knowledge of these host cell requirements not only informs us of the molecular pathways exploited by the virus but also provides further targets that could be pursued for antiviral drug development. Here we use an integrative systems approach, based on genome-wide RNA interference screening, to identify 295 cellular cofactors required for early-stage influenza virus replication.

(Continue . . .)

 

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