Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells.
The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation. We generated an nsp1 mutant (nsp1-mt) that neither promoted host mRNA degradation nor suppressed host protein synthesis in expressing cells. Both a SARS-CoV mutant virus, encoding the nsp1-mt protein (SARS-CoV-mt), and a wild-type virus (SARS-CoV-WT) replicated efficiently and exhibited similar one-step growth kinetics in susceptible cells. Both viruses accumulated similar amounts of virus-specific mRNAs and nsp1 protein in infected cells, whereas the amounts of endogenous host mRNAs were clearly higher in SARS-CoV-mt-infected cells than in SARS-CoV-WT-infected cells, in both the presence and absence of actinomycin D. Further, SARS-CoV-WT replication strongly inhibited host protein synthesis, whereas host protein synthesis inhibition in SARS-CoV-mt-infected cells was not as efficient as in SARS-CoV-WT-infected cells. These data revealed that nsp1 indeed promoted host mRNA degradation and contributed to host protein translation inhibition in infected cells. Notably, SARS-CoV-mt infection, but not SARS-CoV-WT infection, induced high levels of beta interferon (IFN) mRNA accumulation and high titers of type I IFN production. These data demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that SARS-CoV nsp1 most probably plays a critical role in SARS-CoV virulence.
Narayanan
Krishna
K
Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1019, USA. shmakino@utmb.edu
Huang
Cheng
C
Lokugamage
Kumari
K
Kamitani
Wataru
W
Ikegami
Tetsuro
T
Tseng
Chien-Te K
CT
Makino
Shinji
S
D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D009154:Mutation; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000502:physiology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000502:physiology*
D007370:Interferon Type I; D012333:RNA, Messenger; D017361:Viral Nonstructural Proteins; C521592:Nsp1 protein, SARS coronavirus; D012324:RNA-Dependent RNA Polymerase