Assessment of Antiviral Properties of Peramivir against H7N9 Avian Influenza Virus in an Experimental Mouse Model.
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ABSTRACT:
SUBMITTER: Farooqui A
PROVIDER: S-EPMC4649212 | biostudies-literature | 2015 Dec
REPOSITORIES: biostudies-literature
Publications
Assessment of Antiviral Properties of Peramivir against H7N9 Avian Influenza Virus in an Experimental Mouse Model.
Farooqui Amber A Huang Linxi L Wu Suwu S Cai Yingmu Y Su Min M Lin Pengzhou P Chen Weihong W Fang Xibin X Zhang Li L Liu Yisu Y Zeng Tiansheng T Paquette Stephane G SG Khan Adnan A Kelvin Alyson A AA Kelvin David J DJ
Antimicrobial agents and chemotherapy 20150914 12
The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avia ...[more]
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Project description:Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1-9, 2-10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission.
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