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Shades of 1918? New study compares avian flu with a notorious killer from the past
Date:2/10/2009

gton. Using this strategy, respiratory tissue was analyzed with high-throughput technologies of functional genomics, proteomics and transcriptomics to measure gene expression and regulation in fine-grained detail. Such techniques have opened a new window onto the genetic underpinnings of infectious disease.

A large number of these genes code for cytokines and chemokinesimmunomodulating agents which include interleukins, interferons and other factors involved with the host's innate inflammatory response to infection. The result of this overwhelming transcription induction, shown graphically in figure 1, is a "cytokine storm" often leading to acute respiratory distress syndrome in the viral host, while proving entirely ineffective in blunting prodigious replication of the H5N1 virus.

Respiratory tissues sampled on days 1, 2 4 and 7 post-infection were subjected to pathological, viral and microarray analysis. Although the 1918 ressortant strains were found to be highly virulent, they were outmatched by H5N1's rapid onset, overwhelming transcription induction of cytokine and chemokine genes and headlong, sustained viral replication with wider distribution in the lungs. As Baskin notes, referring to the group's measurements of Tissue Culture Infectious Dose or TCID over the course of H5N1's infection, "the take home message is that for H5N1 there is hardly any viable tissue left to infect by day 7, yet there is still very strong viral replication." Further, despite the broad and sustained upregulation of inflammatory genes, they were of no use in limiting the H5N1 infection.

While the new study found that the 1918 ressortant strains and H5N1 each attacked specialized respiratory cells called pneumocytes, the 1918 chimaraes showed preference for so-called type I pneumocytes, responsible for air exchange in the lungs. In contrast, H5N1 characteristically infects the more numerous type II pneumocytes, a critical distinction, as Dr. Baskin explains:
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Contact: Joe Caspermeyer
joseph.caspermeyer@asu.edu
480-727-0369
Arizona State University
Source:Eurekalert  

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