Acute Respiratory Damage Mechanism Of The H5n1 Avian Influenza Virus And The H1n1 Influenza Virus

Due to there is no effective drug, H5N1avian influenza virus caused se-rious damage and mortality can be as high as60%. On the other hand, there are related reports show man-made laboratory bird flu virus can disseminate between ferrets, which alarms we should concern the biological threats comes from recombinant H5N1avian influenza virus. Therefore resolve the patho-genesis of H5N1avian influenza virus, find out the new drug targets is im-minent.In this study, we demostrated that Renin-Angiotensin system(RAS) plaing a key role in the pathogenethsis of acute lung injury induced by H5N1avian influenza virus,especially ACE2protein, the key negative regulator of RAS can be down-regulated by H5N1avian influenza virus and angiotensin II level rised consequently.In other hand, Ace2gene knock out mice show more severe symptoms of acute lung injury, while injection of the recombinant ACE2pro-tein can significantly alleviate the symptoms of acute lung injury. Above all these experiments prove that H5N1avian influenza virus can cause the dis-order of RAS system, especially down-regulated the expression of ACE2protein to cause acute lung injury, and ACE2protein may become new drug for the treatment of H5N1avian influenza virus.At the same time, in this study we also screened and verified the effect of some clinical drugs against H5N1avian influenza virus. Results showed that chlorpromazine, which was the frist psychotropic substance, could prevent but not treat H5N1avian influenza virus. The2009flu pandemic involved the emergence of a new strain of a swine-origin H1N1influenza virus (S-OIV H1N1) that infected almost every country in the world. Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury. In this study, we are the first to de-scribe a mouse model of S-OIV virus infection with acute lung injury and im-mune responses that reflect human clinical disease. The clinical efficacy of the antiviral oseltamivir (Tamiflu) administered in the early stages of S-OIV H1N1infection was confirmed in the mouse model. Moreover, elevated levels of IL-17, Th-17mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing. IL-17deficiency or treatment with monoclonal antibodies against IL-17ameliorated acute lung injury in-duced by the S-OIV H1N1virus in mice. These results suggest that IL-17plays an important role in S-OIV-induced acute lung injury and that monoclonal an-tibodies against IL-17could be useful as a potential therapeutic remedy for future S-OIV H1N1pandemics.