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So far there are at least five coronaviruses that are responsible for human respiratory infections.The pathogenesis and immunity ofcoronavirus are the result of interaction between virus and host.The innate immune response will be started when coronaviruses infect cells.Coronaviruses usually encode multifunctional proteins that are critical for viral replication and blocking the innate immune response to viral infection.Human coronavirus NL63 (HCoV-NL63), a new-emerging human coronavirus for human respiratory infections, has two papain-like protease(PLP) core domains, PLP1 and PLP2, in nonstructural protein nsp3.Besides the proteolytic processing activity towards pp1a(1ab), we have previously demonstrated that PLP2 of HCoV-NL63 has in vitro deubiquitinase (DUB) activity.