Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped single-strand positive-sense RNA virus, is highly contagious, causing mortal respiratory disease. The SARS-CoV RNA genome encodes two different proteases papain-like protease (PLpro) and 3C-like protease (3CLpro), being responsible for proteolytic processes of large replicase polyproteins pp1a and pp1b. PLpro is reported to be an interferon antagonist, being associated with the inhibition of innate immune responses. In this study, we investigated the effects of PLpro on TRL7/8 signaling induced by imiquimod (IMQ). Firstly, expression of PLpro in human promonocyte HL-CZ cells was analyzed Western blotting. In addition, expression of PLpro significantly inhibited IMQ-induced activation of interferon-stimulated response element (ISRE) and Nuclear factor-kappaB（NF-κB）promoters. Furthermore, quantitative real time PCR showed that IMQ induced a significant increase of IL-6, IL-8, PKR, and OAS mRNA expression in vector control cells than those in PLpro-expressing cells. Importantly, Western blotting showed that PLpro inhibited the phosphorylation of p38 MAPK, CREB, IRF-3 and STAT1 in IMQ-induced responses. In this study, SARS-CoV PLpro was firstly reported to block TLR7/8 signaling, being helpful for understanding the SARS pathogenesis.
