title: Identification of Hsp90 as a species independent H5N1 avian influenza A virus PB2 interacting protein.
abstract: The avian influenza polymerase protein PB2 subunit is an important mediator of cross species adaptation and adaptation to mammalian cells is strongly but not exclusively associated with an adaptive mutation of the codon at position 627 of the PB2 protein which alters the glutamate normally found at this position to a lysine. This study sought to identify host cell factors in both mammalian and avian cells that interacted in a species specific or species independent manner. Two PB2 fusion proteins differing only in codon 627 were generated and transfected into mammalian and avian cells and interacting proteins identified through co-immunoprecipitation. A number of proteins including Hsp90 were identified and further investigation showed that Hsp90 interacted with both isoforms of PB2 in both mammalian and avian cells. Hsp90 is thus identified as a species independent interacting protein, further confirming that this protein may be a suitable target for anti-influenza drug development.
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, 25/25 Phuttamontol Sai 4, Salaya 73170, Nakorn Pathom, Thailand.
authors.forename: Krit
authors.initials: K
authors.lastname: Jirakanwisal
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, 25/25 Phuttamontol Sai 4, Salaya 73170, Nakorn Pathom, Thailand.
authors.forename: Kanjana
authors.initials: K
authors.lastname: Srisutthisamphan
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, 25/25 Phuttamontol Sai 4, Salaya 73170, Nakorn Pathom, Thailand.
authors.forename: Chutima
authors.initials: C
authors.lastname: Thepparit
authors.affiliation: Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand.
authors.forename: Ornpreya
authors.initials: O
authors.lastname: Suptawiwat
authors.affiliation: Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand.
authors.forename: Prasert
authors.initials: P
authors.lastname: Auewarakul
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, 25/25 Phuttamontol Sai 4, Salaya 73170, Nakorn Pathom, Thailand; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang 12120, Pathum Thani, Thailand.
authors.forename: Atchara
authors.initials: A
authors.lastname: Paemanee
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang 12120, Pathum Thani, Thailand.
authors.forename: Sittiruk
authors.initials: S
authors.lastname: Roytrakul
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, 25/25 Phuttamontol Sai 4, Salaya 73170, Nakorn Pathom, Thailand. Electronic address: duncan_r_smith@hotmail.com.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D021122:Protein Subunits / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; C057027:PB2 protein, Influenzavirus A; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Avian; Co-immunoprecipitation; Heat shock protein; Interaction; Mammalian; Polymerase