Development of new therapeutics for a highly pathogenic influenza virus infection by inhibition of virus entry and multiplication

我们发现，II型膜结合丝氨酸蛋白酶MSPL/TMPRSS13是进入高致病性禽流感(HPAI)病毒细胞的重要细胞因子。为了证实这一证据，我们制作了TPMRSS13 KO小鼠，并对动物进行了病毒攻击。在TPMRSS13 KO小鼠中，HPAI病毒与血凝素(HA)裂解位点序列RKKR的部分病毒增殖和KKKR序列的完全抑制。结果表明，MSPL/TMPRSS13对于HPAI病毒的入侵是必不可少的。此外，我们发现病毒感染会刺激流感。细胞因子。蛋白水解酶的循环及其在感染所致多器官衰竭的致病机制中起着重要作用。

We found that type II membrane bound serine proteases MSPL/ TMPRSS13 are essential cellular factors for entry into cells of the highly pathogenic avian influenza(HPAI) viruses. To confirm the evidence, we have made TPMRSS13 KO mice and challenged the viruses to the animals. Viral multiplication of the HPAI viruses with the hemagglutinin(HA) cleavage site sequence RKKR partially and the sequence KKKR was completely suppressed in the TPMRSS13 KO mice. The results indicate that MSPL/ TMPRSS13 are essential for the entry of the HPAI virus. Furthermore, we found that viral infection stimulates the influenza. cytokine. protease cycle and the cycle plays an important role in the pathogenicity of multiple organ failure induced by infection.