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Genes Convert Harmless Flu to 1918-Like Flu

Virus can replicate in both upper and lower respiratory tracts

TUESDAY, Jan. 6 (HealthDay News) -- Adding four genes from the 1918 pandemic influenza virus, which may have caused 50 million deaths worldwide, to a relatively harmless contemporary flu virus can convert the virus into a 1918-like virus, according to research published online Dec. 29 in the Proceedings of the National Academy of Sciences.

Tokiko Watanabe, Ph.D., from the University of Wisconsin-Madison, and colleagues generated reassortant viruses between the 1918 pandemic influenza virus and the human K173 virus (a contemporary flu virus isolate with low pathogenicity), to identify genes associated with virulence of the 1918 virus. The reassortant viruses were tested in ferrets, which provide a close model of human influenza infection, according to the authors.

The researchers found that most K173 viruses containing single gene substitutions from the 1918 virus did not markedly alter the pattern of infection, growing in nasal turbinates but not the trachea and lungs. However, a K173 virus carrying the three RNA polymerase genes and the nucleoprotein gene from the 1918 virus became a 1918-like strain, able to replicate in the upper and lower respiratory tracts (nasal turbinates, trachea and lungs) of ferrets.

"Our findings strongly implicate the viral RNA polymerase complex as a major determinant of the pathogenicity of the 1918 pandemic virus," Watanabe and colleagues conclude. "This new insight may aid in identifying virulence factors in future pandemic viruses that could be targeted with antiviral compounds."

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