1. [NP gene of pandemic H1N1 virus attenuates virulence of mouse-adapted human influenza virus].
- Author
-
Zhirnov OP, Syrtsev VV, Schwalm F, and Klenk HD
- Subjects
- Adaptation, Biological, Animals, Birds, Cell Line, Chick Embryo, Humans, Influenza in Birds virology, Influenza, Human virology, Lung virology, Mice, Molecular Sequence Data, Mutant Proteins chemistry, Mutant Proteins genetics, Mutant Proteins metabolism, Nucleocapsid Proteins, Point Mutation, Swine, Virulence genetics, Virus Replication genetics, Caspases metabolism, Genes, Viral, Influenza A Virus, H1N1 Subtype pathogenicity, Influenza A Virus, H1N1 Subtype physiology, RNA-Binding Proteins chemistry, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Viral Core Proteins chemistry, Viral Core Proteins genetics, Viral Core Proteins metabolism
- Abstract
The authors studied a possible role of the caspase cleavage motif located in the nucleoprotein (NP) of pandemic influenza virus H1N1 in the regulation of viral virulence properties. A reverse genetics method was used to obtain chimeric seasonal-like mouse-adapted influenza virus hvA/PE/8/34 (H1N10) carrying either the NP gene of wild type pandemic virus with incomplete caspase motif ETGC or mutated pandemic NP with natural caspase cleavage site of human type ETDG. The wild-type NP gene of the pandemic virus was found to poorly fit to the gene pattern of closely related seasonal-like hvA/PR/8/34 virus (H1N1) and did not rescue mature virus production whereas a mutated NP with human-type caspase cleavage site maintained gene fitness, giving rise to a chimeric virus. The generated chimeric virus hvA/PR/8/34 carrying the mutated pandemic NP successfully replicated in the murine lung, but was attenuated and did not reach the virulence level of seasonal-like mouse-adapted virus hvA/PR/8/34. The findings indicate that the NP caspase cleavage site plays a role in viral adaptation and viral virulence in mammals.
- Published
- 2011