Tuesday, August 24, 2010

Study: What Makes Avian Flu So Deadly




# 4830



Avian flu, particularly H5N1, has our attention because unlike regular influenza, it has a very high mortality rate.  Among those we know to have been infected, roughly 60% have died.


A rate well over 100 times higher than with regular flu.


Roughly 18 months ago we got a look at a study that compared the pathogenesis (disease progression) of non-human primates (macaques) infected with the H5N1 virus, seasonal flu, and with two altered viruses carrying genetic material from the 1918 Spanish Flu.


The study, entitled Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus by Carole Baskin et. al.  appeared PNAS (The Proceedings of the National Academy of Science).


At the time, I wrote a 3-part essay which attempted to put this complex study into layman’s terms. 


For those interested in learning more about the human immune system, cytokine production, and the pathogenesis of influenza the Baskin study and these three blogs may be of value:


Dissecting the Influenza Pathogenesis Study Pt. 1 (link fixed)

Dissecting the Influenza Pathogenesis Study Pt. 2
Dissecting the Influenza Pathogenesis Study Pt. 3


While the Baskin study is fascinating, and gives us considerable insight into what avian flu does to primates, it really doesn’t explain how or why.


To help us with those questions, researchers at Baylor College of Medicine and The University of Texas at Austin have studied the molecular structure of the avian flu virus, and have found 4 tiny amino acids dangling from the tip of a protein called NS1 that they believe at least partially explains this virulence.

Their research appears in the latest issue of the Journal of Virology.  You can access the abstract at the link below.


J. Virol. doi:10.1128/JVI.01278-10

The ESEV PDZ Binding-Motif of the Avian Influenza A Virus NS1 Protein Protects Infected Cells from Apoptosis through Directly Targeting Scribble


Hongbing Liu, Lisa Golebiewski, Eugene C. Dow, Robert M. Krug, Ronald T. Javier, and Andrew P. Rice


Admittedly, to non-scientists, this title is more than a little imposing.  


Apoptosis is programmed cellular death, while Scribble is a protein the body’s immune system uses to promote the early death (apoptosis) of virally infected cells. 


In this way, the immune system can help limit viral replication while it develops defenses (antibodies, cytokines, etc.) against the invader.


In the case of H5N1, the virus’s PDZ binding-motif works to  deactivates the host’s apoptosis defense mechanism, giving the virus a decided advantage.


Fortunately, for us mere mortals without a virology degree, we have a less technical background piece from the BCM news site which is well worth following the link and reading in its entirety. 



Avian flu virus protein turns off cell defense

HOUSTON -- (August 23, 2010) -- As the avian influenza A virus seeks to infect its bird hosts, it brings a special weapon to the fray – four tiny amino acids that hang off the end of a viral protein called NS1, said researchers from Baylor College of Medicine (www.bcm.edu) and The University of Texas at Austin in a report that appears in the current Journal of Virology.


This collection of molecules known as the PDZ binding-motif help make the avian virus – known to experts at H5N1 – particularly virulent and a threat to human populations everywhere.

(Continue . . . )