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Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection.

Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection.
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Pascua PNQ, Mostafa HH, Marathe BM, Vogel P, Russell CJ, Webby RJ, Govorkova EA,


Pascua PNQ, Mostafa HH, Marathe BM, Vogel P, Russell CJ, Webby RJ, Govorkova EA, (click to view)

Pascua PNQ, Mostafa HH, Marathe BM, Vogel P, Russell CJ, Webby RJ, Govorkova EA,

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Scientific reports 2017 08 047(1) 7345 doi 10.1038/s41598-017-07433-z
Abstract

Influenza B viruses are important human pathogens that remain inadequately studied, largely because available animal models are poorly defined. Here, we developed an immunocompromised murine models for influenza B virus infection, which we subsequently used to study pathogenicity and to examine antiviral efficacy of the neuraminidase inhibitor peramivir. We studied three influenza B viruses that represent both the Yamagata (B/Massachusetts/2/2012 and B/Phuket/3073/2013) and Victoria (B/Brisbane/60/2008, BR/08) lineages. BR/08 was the most pathogenic in genetically modified immunocompromised mice [BALB scid and non-obese diabetic (NOD) scid strains] causing lethal infection without prior adaptation. The immunocompromised mice demonstrated prolonged virus shedding with modest induction of immune responses compared to BALB/c. Rather than severe virus burden, BR/08 virus-associated disease severity correlated with extensive virus spread and severe pulmonary pathology, stronger and persistent natural killer cell responses, and the extended induction of pro-inflammatory cytokines and chemokines. In contrast to a single-dose treatment (75 mg/kg/day), repeated doses of peramivir rescued BALB scid mice from lethal challenge with BR/08, but did not result in complete virus clearance. In summary, we have established immunocompromised murine models for influenza B virus infection that will facilitate evaluations of the efficacy of currently available and investigational anti-influenza drugs.

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