Sars Coronavirus, The H5n1 Avian Influenza Virus Pathogenesis Of The Study

The Severe Acute Respiratory Syndrome(SARS) was a worldwide epidemic disease which happened last few years,the pathogen of this disease was a new kind of RNA single strand virus,SARS-associated coronavirus,which could cause progressive respiratory failure and even death.SARS-Cov encoded four main strcutural proteins and the most important one was the spike protein,which involved in the binding,fusion and entry between the virus and the receptor in the hostcell,it was the primary target of the host's immune system and contained the main neutralizing antigens.We expressed and purified nearly full length spike protein and its mutants in mammalian cells by using a series of molecular clonning technology and the high throughput mammalian cell protein expression system, with the Angiotesin Converting Enzyme 2(ACE2) gene knock-out mice model,we proved that the ACE2 was the crucial receptor for SARS-Cov in vivo.SARS-CoV entered the host cell through the binding between the spike protein and ACE2, caused,the downregulation of the ACE2 expression and affected the renin-angiotensin system balance,finally initiated or aggravated acute lung injury. The core receptor binding domain located from the 318 to 510 amino acid of the spike protein,the mutant protein only contain this domain could induce ACE2 downregulation andacute lung injury.The avian influenza virus subtype H5N1 isolated from a human was a newly mutated virus most of the patients suffred from fever,cough,nasal mucus and usually accompanied with severe lung injury.Autophagy was characterized as a kind of programmed cell death.We used H5N1 avian influenza virus,inactivate H5N1 avian influenza virus and recombined H5 protein to treat the Hela and A549 cells,and found all of them could induce autophagy in a different level by the means of electron microscope,this result was also confirmed by the confocol experiment of the aggregation of the MAP1LC3,the autophagy,marker.We proved that the virus induced autophagy through the P38-TSC2-mTOR signaling pathway with the help of RNA interference technology.Futhermore,we confirmed that the H5N1 avian influenza virus could induce acute lung injury in mice.