Abstract
SARS-CoV and SARS-CoV-2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C-like cysteine protease (3CL pro ) and papain-like protease (PL pro ) into 16 nonstructural proteins (nsps). PL pro is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2, between nsp2/3 and between nsp3/4 with recognition motif of LXGG, and the sites in the C-terminus of ubiquitin and of protein interferon-stimulated gene 15 (ISG15) with recognition motif of RLRGG. Alone or together with SARS unique domain (SUD), PL pro can stabilize an E3 ubiquitin ligase, the ring-finger, and CHY zinc-finger domain-containing 1 (RCHY1), through domain interaction, and thus, promote RCHY1 to ubiquitinate its target proteins including p53. However, a dilemma appears in terms of PL pro roles. On the one hand, the ubiquitination of p53 is good for SARS-CoV because the ubiquitinated p53 cannot inhibit SARS-CoV replication. On the other hand, the ubiquitination of NF-κB inhibitor (IκBα), TNF receptor-associated factors (TRAFs), and stimulator of interferon gene (STING), and the ISGylation of targeted proteins are bad for SARS-CoV because these ubiquitination and ISGylation initiate the innate immune response and antiviral state. This mini-review analyzes the dilemma and provides a snapshot on how the viral PL pro smartly manages its roles to avoid its simultaneously contradictory actions, which could shed lights on possible strategies to deal with SARS-CoV-2 infections.
Keywords: ISG15; PLpro; SARS-CoV; SARS-CoV-2; p53; ubiquitin.
【저자키워드】 SARS-CoV-2, SARS-CoV, PLPro, ISG15, p53, ubiquitin, 【초록키워드】 Zinc, innate immune response, Antiviral, interferon, 3CL pro, protease, Replication, Papain-like protease, Protein, accessory proteins, Viral, nsp1, envelope, membrane, nonstructural protein, Nsp3, pp1a, PLPro, inhibitor, SARS-CoV-2 infections, accessory protein, STING, NF-κB, TNF, Interaction, ISG15, Nsps, can not, cysteine, Factor, domain, cysteine protease, Nucleocapsid proteins, Papain, dilemma, C-terminus, motif, E3 ubiquitin ligase, IκBα, CoV replication, interferon-stimulated gene, ubiquitin, polyprotein, polyproteins, pp1ab, stimulator, autocleavage, its target proteins, RCHY1, inhibit, appear, provide, unique, promote, released, cleaved, cleave, its target protein,