Retinoic acid inducible gene I Activates innate antiviral response against human parainfluenza virus type 3

Abstract

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-α/β) and tumor necrosis factor-α (TNFα activated by NFκB) 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 TNFα and IFNβ 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 IFNβ (via activation of interferon regulatory factor-3 or IRF3) and TNFα (via activation of NF-κB).

Learning from the Messengers: Innate Sensing of Viruses and Cytokine Regulation of Immunity — Clues for Treatments and Vaccines

“…RIG-I is sensor for shorter dsRNA and 5’ppp ssRNAs and mediates type I IFN responses in response to a number of viruses, including HIV-1, influenza A virus, EBV, RSV, reovirus, VV, Sendai virus, and human parainfluenza virus [35,90,91,91,92,93,94,95,97,98,101,102,134,143]. In addition to mediating IFN and proinflammatory cytokine production, RIG-I has also been shown to mediate activation of the inflammasome and thus IL-1β secretion in respond to the rhabdovirus VSV [103].…”

Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX3X is Central to its Role in Antiviral Immunity

“…DDX3X is crucial in regulating innate antiviral immune responses initiated by the retinoic-acid-inducible gene I (RIG-I)-like receptors (RLRs) [1]. RLRs recognize cytoplasmic RNA derived from viruses such as hepatitis C (HCV), influenza A, human immunodeficiency virus type 1 (HIV-1) [2], and parainfluenza virus type 3 (hPIV-3) [3], a major cause of bronchiolitis, bronchitis, and pneumonia in children, the elderly, and immunocompromised, and a cause of significant mortality in hematopoietic stem cell transplant recipients [4,5]. Despite being an important respiratory pathogen with no regulatory-approved vaccine or antiviral available, little is known of the host factors that mediate the response to hPIV-3 infection.…”

Impaired virus replication and decreased innate immune responses to viral infections in nasal epithelial cells from patients with allergic rhinitis

“…A study by Sabbah et al . demonstrated that PIV3 infection in A549 (human respiratory epithelial cells) caused induction of IFN‐β through the activation of IFN regulatory factor 3 (IRF3). In parallel with IFNs, proinflammatory cytokines, including regulated on activation, normal T expressed and secreted (RANTES), are generated by the airway epithelial cells in response to virus infection .…”

“…Similarly, intracellular TLRs in the airway epithelial cells, which sense viral RNA, seem to be involved in IFN production during infection with respiratory viruses such as rhinovirus [28] and influenza A virus [29], as well as respiratory syncytial virus (RSV), that belongs to paramyxoviruses [30]. A study by Sabbah et al [31] demonstrated that PIV3 infection in A549 (human respiratory epithelial cells) caused induction of IFN-b through the activation of IFN regulatory factor 3 (IRF3). In parallel with IFNs, proinflammatory cytokines, including regulated on activation, normal T expressed and secreted (RANTES), are generated by the airway epithelial cells in response to virus infection [32,33].…”