tetano
Editor, Senior Moderator
J Gen Virol. 2010 Mar 17. [Epub ahead of print]
Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus.
Hale BG, Steel J, Manicassamy B, Medina RA, Ye J, Hickman D, Lowen AC, Perez DR, Garcia-Sastre A.
Mount Sinai School of Medicine;
The 'classical' swine H1N1 influenza A virus lineage was established after the devastating 1918 human pandemic virus entered domestic pig herds. A descendent of this lineage recently re-emerged in humans as the 2009 pandemic H1N1 virus. Adaptation in pigs has lead to several changes in the multifunctional viral NS1 protein as compared with the parental 1918 virus, most notably a K217E substitution that abolishes binding to host Crk/CrkL signaling adapters, and an 11 amino-acid C-terminal truncation. Using reverse genetics, we re-introduced both these features into a prototype 2009 H1N1 strain, A/California/04/09. Restoration of Crk/CrkL binding or extension of NS1 to 230 amino-acids had no impact on virus replication in human or swine cells. In addition, minimal effects on replication, pathogenicity and transmission were observed in mouse and ferret models. Our data suggest that the currently circulating 2009 H1N1 virus is optimized to replicate efficiently without requiring certain NS1 functions.
PMID: 20237225 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20237225?dopt=Abstract
Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus.
Hale BG, Steel J, Manicassamy B, Medina RA, Ye J, Hickman D, Lowen AC, Perez DR, Garcia-Sastre A.
Mount Sinai School of Medicine;
The 'classical' swine H1N1 influenza A virus lineage was established after the devastating 1918 human pandemic virus entered domestic pig herds. A descendent of this lineage recently re-emerged in humans as the 2009 pandemic H1N1 virus. Adaptation in pigs has lead to several changes in the multifunctional viral NS1 protein as compared with the parental 1918 virus, most notably a K217E substitution that abolishes binding to host Crk/CrkL signaling adapters, and an 11 amino-acid C-terminal truncation. Using reverse genetics, we re-introduced both these features into a prototype 2009 H1N1 strain, A/California/04/09. Restoration of Crk/CrkL binding or extension of NS1 to 230 amino-acids had no impact on virus replication in human or swine cells. In addition, minimal effects on replication, pathogenicity and transmission were observed in mouse and ferret models. Our data suggest that the currently circulating 2009 H1N1 virus is optimized to replicate efficiently without requiring certain NS1 functions.
PMID: 20237225 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20237225?dopt=Abstract
