Antibody-Mediated Porcine Reproductive and Respiratory Syndrome Virus Infection Downregulates the Production of Interferon-α and Tumor Necrosis Factor-α in Porcine Alveolar Macrophages via Fc Gamma Receptor I and III

Abstract

Antibody-dependent enhancement (ADE) contributes to the pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV)-persistent infection. However, the mechanisms of PRRSV-ADE infection are still confusing. A clear understanding of the event upon virus infection by the ADE pathway has become crucial for developing efficient intervention of the PRRSV infection. In this study, an ADE assay showed that PRRSV-ADE infection in porcine alveolar macrophages (AMs) significantly decreased the production of interferon-α (IFN-α) and tumor necrosis factor-α (TNF-α), and significantly increased the production of interleukine-10 (IL-10). A gene knockdown assay based on small interfering RNA (siRNA) showed that both Fc gamma receptor I (FcγRI) and FcγRIII in porcine AMs were involved in PRRSV-ADE infection. An activation assay showed that specific activation of FcγRI or FcγRIII in porcine AMs during PRRSV infection not only significantly decreased the production of IFN-α and TNF-α, but also significantly increased the production of IL-10 and significantly facilitated PRRSV replication. In conclusion, our studies suggested that ADE downregulated the production of IFN-α and TNF-α in porcine AMs maybe via FcγRI and FcγRIII, thereby leading to enhanced PRRSV infection.

Ross River Virus Immune Evasion Strategies and the Relevance to Post-viral Fatigue, and Myalgic Encephalomyelitis Onset

“…As well as the downregulation of proinflammatory - antiviral gene expression, IL-10 expression was significantly increased, as was the transcription factor Sp1 ( 36 , 37 ). Similar patterns were also detected in a flavivirus (DEN) ( 38 – 42 ) and an arterivirus (PRRSV) ( 43 – 46 ). Post-ADE IL-12 and IFN-γ suppression was also observed for DEN, as well as concomitant impacts on the associated transcription factors (e.g., STAT, IRF), while IL-10 expression was similarly unaffected or increased ( Table 1 ).…”

Differences in Humoral Immune Response against the Type 2 Porcine Reproductive and Respiratory Syndrome Virus via Different Immune Pathways

“…Piglets in test groups were inoculated with 10 6 TCID 50 PRRSV HeN-3 through intranasal and intramuscular inoculation (in nape) respectively, and piglets in the control group were inoculated with equal volumes of the cell culture medium. Serum and saliva in all the groups were respectively collected for viral loads and antibody titers at 0, 3,7,11,15,19,23,27,31,35,39, and 43 dpi. At 43 dpi, the PAMs, submandibular lymph nodes, and inguinal lymph nodes of piglets were obtained for viral loads detection after necropsy under clean conditions.…”

“…The PRRSV infection usually induces an inadequate or absent host immune response by inhibiting IFN-α production [ 13 , 14 ], while HeN-3 exhibited different responses. Our previous studies have revealed that the field virus HeN-3 caused a high IFN-α production in PAMs during early infection and slightly inhibited IFN-α production in PAMs during late infection [ 15 ]. Moreover, HeN-3 can induce the production of IFN-α in piglets in the first 15 dpi [ 16 ].…”

PharmGKB summary: heparin-induced thrombocytopenia pathway, adverse drug reaction

“…Recent data suggest that release of neutrophil extracellular traps following neutrophil activation via the FcγRIIa receptor is a causative factor in HIT-associated thrombosis (HITT) [16]. In macrophages, FCGR1A and FCGR3A have been linked to release of IL-10, an important immunoregulatory cytokine that may have relevant downstream effects in HIT [17,18]. Current models for HIT indicate that a yet unidentified antigen exposure happens prior to heparin exposure, creating a primary immune response that primes production of relevant IgGs.…”