Comparative Activities of Oseltamivir and A-322278 in Immunocompetent and Immunocompromised Murine Models of Influenza Virus Infection
作者： Michael G. Ison , Vasiliy P. Mishin , Thomas J. Braciale , Frederick G. Hayden , Larisa V. Gubareva
DOI: 10.1086/500464
关键词: Virology 、 Orthomyxoviridae 、 Viral disease 、 Virus 、 Hemagglutinin (influenza) 、 Oseltamivir 、 Microbiology 、 Viral replication 、 Neuraminidase 、 Biology 、 Severe combined immunodeficiency
摘要: We developed an immunocompromised murine model of influenza virus infection and demonstrated comparable efficacy oral oseltamivir A-322278 (both given at dosages 10 mg/kg/day) in reducing viral replication, decreasing weight loss, prolonging survival. Once the treatment was discontinued, severe combined immunodeficient (SCID) mice had progressive replication clinical decline. Drug-resistant variants were detected 4 (29%) 14 2 (13%) 15 BALB/c SCID) treated with or A-322278, respectively; no resistant placebo-treated mice. Amino acid substitutions hemagglutinin receptor-binding site aa 137 225 cloned isolates. A substitution neuraminidase (NA) active (Arg292Lys) recovered from oseltamivir-treated mouse. This would be useful for elucidation molecular mechanisms resistance to NA inhibitors testing anti-influenza therapy options that might prevent emergence variants.
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