PDF(Pubmed)
Abstract：
Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) has been harming the pig industry worldwide for nearly 40 years. Although scientific researchers have made substantial efforts to explore PRRSV pathogenesis, the immune factors influencing PRRSV infection still need to be better understood. Infectious virus-antibody immune complexes (ICs) formed by PRRSV and sub-or non-neutralizing antibodies specific for PRRSV may significantly promote the development of PRRS by enhancing PRRSV replication through antibody-dependent enhancement. However, nothing is known about whether PRRSV infection is affected by non-infectious ICs (NICs) formed by non-pathogenic/infectious antigens and corresponding specific antibodies. Here, we found that PRRSV significantly induced the transcripts and proteins of interferon-α (IFN-α), IFN-β, IFN-γ, IFN-λ1, and tumor necrosis factor-α (TNF-α) in vitro primary porcine alveolar macrophages (PAMs) in the early stage of infection. Our results showed that NICs formed by rabbit-negative IgG (RNI) and pig anti-RNI specific IgG significantly reduced the transcripts and proteins of IFN-α, IFN-β, IFN-γ, IFN-λ1, and TNF-α in vitro PAMs and significantly elevated the transcripts and proteins of interleukine-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in vitro PAMs. NICs-mediated PRRSV infection showed that NICs not only significantly decreased the induction of IFN-α, IFN-β, IFN-γ, IFN-λ1, and TNF-α by PRRSV but also significantly increased the induction of IL-10 and TGF-β1 by PRRSV and considerably enhanced PRRSV replication in vitro PAMs. Our data suggested that NICs could downregulate the production of antiviral cytokines (IFN-α/β/γ/λ1 and TNF-α) during PRRSV infection in vitro and facilitated PRRSV proliferation in its host cells by inhibiting innate antiviral immune response. This study elucidated one novel immune response to PRRSV infection, which would enhance our understanding of the pathogenesis of PRRSV.
摘要：
由PRRS病毒（PRRSV）引起的猪繁殖与呼吸综合征（PRRS）已危害全球养猪业近40年。尽管科学研究人员已经做出了巨大的努力来探索PRRSV的发病机制，影响PRRSV感染的免疫因素仍需进一步了解。由PRRSV和PRRSV特异性的亚或非中和抗体形成的感染性病毒-抗体免疫复合物（IC）可能通过抗体依赖性增强来增强PRRSV复制，从而显着促进PRRS的发展。然而,目前尚不清楚PRRSV感染是否受非致病性/感染性抗原和相应特异性抗体形成的非感染性IC(NIC)的影响.这里,我们发现PRRSV显著诱导干扰素-α（IFN-α）的转录本和蛋白质，IFN-β,IFN-γ，IFN-λ1和肿瘤坏死因子-α（TNF-α）在感染早期的体外原代猪肺泡巨噬细胞（PAMs）中的作用。我们的结果表明，兔阴性IgG（RNI）和猪抗RNI特异性IgG形成的NIC显着降低了IFN-α的转录本和蛋白质，IFN-β,IFN-γ，IFN-λ1和TNF-α在体外PAMs和显着升高白细胞介素-10（IL-10）和转化生长因子-β1（TGF-β1）的转录本和蛋白。NIC介导的PRRSV感染表明，NIC不仅显着降低了IFN-α的诱导，IFN-β,IFN-γ，PRRSV的IFN-λ1和TNF-α，但也显着增加了PRRSV对IL-10和TGF-β1的诱导，并显着增强了PRRSV在体外PAMs中的复制。我们的数据表明，NIC可以在体外PRRSV感染期间下调抗病毒细胞因子（IFN-α/β/γ/λ1和TNF-α）的产生，并通过抑制先天抗病毒免疫反应促进PRRSV在宿主细胞中本研究阐明了一种针对PRRSV感染的新型免疫反应，这将增强我们对PRRSV发病机制的认识。
