Potent Inhibition of SARS-Associated Coronavirus (SCoV) Infection and Replication by Type I Interferons (IFN-α/β) but Not by Type II Interferon (IFN-γ)

Abstract

We sought to investigate the anti-severe acute respiratory syndrome (SARS)-associated coronavirus (SCoV) activities of type I (alpha and beta) and type II (gamma) interferons (IFN) in vitro. Type I IFNs protected cells from cytopathic effects (CPE) induced by SCoV, and inhibited viral genomic RNA replication in FRhk-4 cells (measured by quantitative RT-PCR) in a dose-dependent manner. Intracellular viral RNA copies were reduced 50% by IFN-alpha at a concentration of 25 U/ml and by IFN-beta at a concentration of 14 U/ml. IFN-gamma had fewer effects on inhibition of viral infection and replication. The type I IFN receptor signaling pathway in host cells is mainly involved in the inhibition of SCoV infection and replication. Type I IFNs could be used as potential agents for anti-SARS treatment.

SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism

“…However, SARS-CoV infection does not result in IFN production in many cell cultures and pretreatment of cells with IFN blocks SARS-CoV infection [13,[24][25][26]. The N protein of SARS-CoV was found to inhibit the activation of IRF-3 and NF-jB induced by SenV, resulting in inhibition of IFN synthesis [8].…”

MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment

“…In particular, the SARS-CoV ORF6 protein is known to inhibit IFN-induced JAK-STAT signalling by blocking the nuclear translocation of phosphorylated STAT1 (p-STAT1), which contributes to the pathogenic potential of the virus in a mouse model (Sims et al , 2013). In spite of these immune evasion strategies, treatment with type I IFNs can inhibit CoV replication in vitro (Garlinghouse et al , 1984; Haagmans et al , 2004; Paragas et al , 2005; Taguchi & Siddell, 1985; Zheng et al , 2004) and, for example, protects type I pneumocytes against SARS-CoV infection in macaques (Haagmans et al , 2004). …”

Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus

“…Among the proteins, N, as the RNA-binding protein, play an important role in both virus RNA synthesis and modulating host cell processes, and phosphorylation may regulate these processes by exposing various functional motifs [4,5]. Several other functions have been postulated for the coronavirus N protein throughout the virus life cycle, including encapsidation, packaging, correct folding of the RNA molecule, the deregulation of the host cell cycle [6,7,8], inhibition of interferon production [9,10], up-regulation of COX2 production [11,12], up-regulation of AP1 activity [13], induction of apoptosis [14,15,16], association with host cell proteins [17], and RNA chaperone activity [18]. Therefore, it is clear that N is a multifunctional protein involved in biological processes related to the survival of PEDV.…”