The Immune Escape Mechanism Of Influenza Virus NS1 Protein And SARS Coronavirus N Protein

Influenza A viruses belong to Orthomyxoviridae,the influenza virus.The RNA genome contains eight independent strands of negative RNA with different sizes,including nonstructural protein 1(NS1)which is encoded by NS gene.NS1 has two main domains,N-terminal RNA-binding domain,involving in RNA binding.C-terminal effect domain,which interacts with a variety of proteins in host cells.NS1 protein is a multi-functional protein during viral infection.NS1 protein binds viral dsRNA and blocks the identification of pathogen associated molecular patterns,suppress translation of host mRNA and regulates cell apoptosis to implement the efficient replication and infection.Virus and host together determine the procession of virus infection.2009 pandemic influenza virus has higher infection rate but lower pathogenic rate than previous high lethal flu,characterized by severe infection mainly affects young adults.We found that the 2009 NS1 and traditional NS1 are in obviously different groups through system evolution analysis and sequence comparison.Further analysis of NS1 amino acid sequence,we found that the NS1 protein of 2009 pandemic influenza virus was conservative in 6,78,98,119,129 and 171 amino acid sites.We found that the 171 th site may play an important role with further study.In the pandemic 2009 flu virus,when the amino acid of the 171 site is Y(Tyrosine),it can enhance the transcription activity of NF-kB.The results of the corresponding PR8 virus NS1 verified the same function.The expression of pandemic influenza virus NS1 protein can promote the integral ubiquitin level and the RIG-I K63 ubiquitination.A549 cells infected with mutational recombinant viruses showed higher cell apoptosis corresponds to lower pathogenicity of 2009 wt flu virus.SARS-Coronavirus(SARS-CoV)is the etiologic agent of Severe Acute Respiratory Syndrome,an emerging disease characterized by atypical pneumonia that arises by an unclear mechanism,and the nucleocapsid protein(N protein)plays important roles in viral infection by inhibiting type I interferon production.In this study,the N protein was demonstrated interaction with TRIM25 and interfered the interaction between TRIM25 and RIG-I which suppressed TRIM25 mediated ubiquity modification of RIG-I.Production of type I interferon was thus inhibited by the N protein.RIG-I ubiquitination could be rescued by overexpression of TRIM25.Our findings provided insightful information on the mechanism by which the N protein of SARS-CoV suppresses host innate immunity.The outbreak of SARS in 2002 uncovered the harm of coronavirus.In 2012,outbreak of Middle East respiratory syndrome coronavirus(MERS-CoV)punctuated the panic.The research of virus’ participation in the immune escape can make us better understand the virus pathogenic mechanism and better prediction,prevention and treatment of virus infection.This study identified NS1 new pathogenic sites and uncovered the mechanism of interferon inhibitation by SARS-CoV N protein.Further research may ultimately help us understand the virus pathogenic mechanism and the details of the micro-host interaction.