title: Human Heat shock protein 40 (Hsp40/DnaJB1) promotes influenza A virus replication by assisting nuclear import of viral ribonucleoproteins.
abstract: A unique feature of influenza A virus (IAV) life cycle is replication of the viral genome in the host cell nucleus. The nuclear import of IAV genome is an indispensable step in establishing virus infection. IAV nucleoprotein (NP) is known to mediate the nuclear import of viral genome via its nuclear localization signals. Here, we demonstrate that cellular heat shock protein 40 (Hsp40/DnaJB1) facilitates the nuclear import of incoming IAV viral ribonucleoproteins (vRNPs) and is important for efficient IAV replication. Hsp40 was found to interact with NP component of IAV RNPs during early stages of infection. This interaction is mediated by the J domain of Hsp40 and N-terminal region of NP. Drug or RNAi mediated inhibition of Hsp40 resulted in reduced nuclear import of IAV RNPs, diminished viral polymerase function and attenuates overall viral replication. Hsp40 was also found to be required for efficient association between NP and importin alpha, which is crucial for IAV RNP nuclear translocation. These studies demonstrate an important role for cellular chaperone Hsp40/DnaJB1 in influenza A virus life cycle by assisting nuclear trafficking of viral ribonucleoproteins.
authors.affiliation: School of Science, Monash University, Subang Jaya, Selangor, 47500, Malaysia.|Virology Group, International Centre for Genetic Engineering &Biotechnology, New Delhi, 110067, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Batra
authors.affiliation: Virology Group, International Centre for Genetic Engineering &Biotechnology, New Delhi, 110067, India.
authors.forename: Shashank
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta GA, 30333, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta GA, 30333, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta GA, 30333, USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta GA, 30333, USA.
authors.forename: Renu B
authors.initials: RB
authors.lastname: Lal
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta GA, 30333, USA.
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
authors.affiliation: School of Science, Monash University, Subang Jaya, Selangor, 47500, Malaysia.|Virology Group, International Centre for Genetic Engineering &Biotechnology, New Delhi, 110067, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Lal
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D055785:Gene Knockdown Techniques; D050956:HSP40 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism* / Q000502:physiology; D007251:Influenza, Human / Q000378:metabolism / Q000821:virology; D008954:Models, Biological; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D011760:Pyrrolidinones / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D001559:Benzhydryl Compounds; D050956:HSP40 Heat-Shock Proteins; C410027:KNK 437; D011760:Pyrrolidinones; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; D014764:Viral Proteins