title: Dengue virus infection activates cellular chaperone Hsp70 in THP-1 cells: downregulation of Hsp70 by siRNA revealed decreased viral replication.
abstract: The pathogenic mechanism of dengue virus infection is related to the host responses within target cells, and therefore we assessed intracellular changes in stress proteins following dengue virus infection. This study provides evidence that Hsp70 helps in viral multiplication by suppressing the type 1 interferon response. Dengue virus infection in human monocytic THP-1 cells led to overexpression of Hsp70, which also acts as a chaperone. The functional role of Hsp70 in dengue virus multiplication was identified by downregulating the Hsp70 gene with its specific siRNA duplexes, which led to a decrease in viral RNA copy numbers in cellular supernatants and intracellular viral load. It also resulted in an increased IFN-α level, which mediates its antiviral effect through double-stranded RNA-induced protein kinase-PKR. Collectively these results suggest that an increased level of Hsp70 expression in dengue-virus-infected THP-1 cells assists in viral replication by escaping the antiviral effect of type 1 interferon.
authors.affiliation: Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Timarpur, Delhi, India.
authors.forename: Y S
authors.initials: YS
authors.lastname: Padwad
authors.forename: K P
authors.initials: KP
authors.lastname: Mishra
authors.forename: Monika
authors.initials: M
authors.lastname: Jain
authors.forename: S
authors.initials: S
authors.lastname: Chanda
authors.forename: L
authors.initials: L
authors.lastname: Ganju
mesh_terms: D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D003716:Dengue Virus / Q000502:physiology*; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; D034622:RNA Interference; D012327:RNA Virus Infections; D034741:RNA, Small Interfering; D015854:Up-Regulation; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000502:physiology*; D019892:eIF-2 Kinase / Q000096:biosynthesis
chemical_list: D018840:HSP70 Heat-Shock Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D019892:eIF-2 Kinase