Emerging and re-emerging human viral pathogens, such as severe acute respiratory syndrome (SARS), which emerged in 2003, and the recently emerged swine-origin H1N1 influenza virus, which causes global pandemics, have had a worldwide impact and therefore represent a serious threat to human health. Viruses as the obligate parasites strictly depend on host cells for replication and, throughout co-evolution with hosts, viruses have developed strategies to evade and subvert the host antiviral innate immune response. A wide variety of RNA viruses have been reported to encode proteins that inhibit host innate immune responses. Papain-like protease (PLP) of human coronavirus is a novel viral-encoded deubiquitinase and is an IFN antagonist for inhibition of host antiviral innate immune response through disruption of ERIS (also called MITA/STING)-mediated signaling. The novel mechanisms by which human coronavirus inhibits host IFN response and new findings that papain-like protease (PLP) of coronavirus is an IFN antagonist which targets specific components of the IFN induction pathway were introduced.