Dengue virus infection induces upregulation of hn RNP-H and PDIA3 for its multiplication in the host cell.
The pathogenic mechanism of Dengue virus (DENV) infection is related to the host responses within target cells and therefore, we assessed intracellular changes in host cell proteins following DENV infection. This study provides evidence that heterogeneous nuclear ribonucleoprotein H (hnRNP-H) and protein disulfide isomerase A3 (PDIA3) helps in DENV multiplication by suppressing TNF-α production in human monocytic THP1 cells. Proteomic analysis of infected cells, identified upregulation of the host cell proteins PDIA3 and hnRNP-H in comparison to mock infected cells. The functional role of hnRNP-H and PDIA3 in DENV infection was identified by down regulating hnRNP-H and PDIA3 genes with their specific siRNA duplexes which lead to decreased intracellular viral load. It also resulted in increased TNF-α level which mediates antiviral effect. This is the first study, which reports the role of PDIA3 and hnRNP-H in TNF-α production in DENV infected cells. Collectively, these results suggest that increased level of hnRNP-H and PDIA3 expression in DENV infected THP1 cells assist in the viral replication by suppressing the TNF-α production.
Immunomodulation Laboratory, Defence Institute of Physiology & Allied Sciences, Lucknow Road, Timarpur, Delhi-110054 India. kpmpgi@rediffmail.com
K P
KP
Mishra
Shweta
Drishya
D
Diwaker
Lilly
L
Ganju
D000998:Antiviral Agents / Q000037:antagonists & inhibitors; D002460:Cell Line; D003716:Dengue Virus / Q000472:pathogenicity*; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000096:biosynthesis*; D054884:Host-Pathogen Interactions; D006801:Humans; D009000:Monocytes / Q000821:virology; D019704:Protein Disulfide-Isomerases / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D015854:Up-Regulation
D000998:Antiviral Agents; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D014409:Tumor Necrosis Factor-alpha; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human