Retinoic acid inducible gene I activates innate antiviral response against human parainfluenza virus type 3.
Human parainfluenza virus type 3 (HPIV3) is a respiratory paramyxovirus that infects lung epithelial cells to cause high morbidity among infants and children. To date, no effective vaccine or antiviral therapy exists for HPIV3 and therefore, it is important to study innate immune antiviral response induced by this virus in infected cells. Type-I interferons (IFN, interferon-alpha/beta) and tumor necrosis factor-alpha (TNFalpha activated by NFkappaB) are potent antiviral cytokines that play an important role during innate immune antiviral response. A wide-spectrum of viruses utilizes pattern recognition receptors (PRRs) like toll-like receptors (TLRs) and RLH (RIG like helicases) receptors such as RIGI (retinoic acid inducible gene -I) and Mda5 to induce innate antiviral response. Previously it was shown that both TNFalpha and IFNbeta are produced from HPIV3 infected cells. However, the mechanism by which infected cells activated innate response following HPIV3 infection was not known. In the current study, we demonstrated that RIGI serves as a PRR in HPIV3 infected cells to induce innate antiviral response by expressing IFNbeta (via activation of interferon regulatory factor-3 or IRF3) and TNFalpha (via activation of NF-kappaB).
Sabbah
Ahmed
A
Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. sabbah@uthscsa.edu
Bose
Santanu
S
D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000378:metabolism; D010224:Parainfluenza Virus 3, Human / Q000276:immunology*; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases