title: Heterologous SH3-p85beta inhibits influenza A virus replication.
abstract: Phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway can support the replication of influenza A virus through binding of viral NS1 protein to the Src homology 3 (SH3) domain of p85beta regulatory subunit of PI3K. Here we investigated the effect of heterologously overexpressed SH3 on the replication of different influenza A virus subtypes/strains, and on the phosphorylation of Akt in the virus-infected cells. We found that heterologous SH3 reduced replication of influenza A viruses at varying degrees in a subtype/strain-dependent manner and SH3 overexpression reduced the induction of the phosphorylation of Akt in the cells infected with PR8(H1N1) and ST364(H3N2), but not with ST1233(H1N1), Ph2246(H9N2), and Qa199(H9N2). Our results suggest that interference with the NS1-p85beta interaction by heterologous SH3 can be served as a useful antiviral strategy against influenza A virus infection.
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China.
authors.forename: Dan-gui
authors.initials: DG
authors.lastname: Zhang
authors.forename: Wei-zhong
authors.initials: WZ
authors.lastname: Li
authors.forename: Ge-fei
authors.initials: GF
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Su
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiang-xing
authors.initials: XX
authors.lastname: Zeng
authors.forename: Xiao-xuan
authors.initials: XX
authors.lastname: Chen
authors.forename: Yan-xuan
authors.initials: YX
authors.lastname: Xu
authors.forename: Kang-sheng
authors.initials: KS
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D015536:Down-Regulation; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D018909:src Homology Domains
chemical_list: C085820:INS1 protein, influenza virus; D021122:Protein Subunits; D017361:Viral Nonstructural Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt