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/TMPRSS 13是高致病性禽流感病毒（HPAI）进入细胞的必需细胞因子。为了证实这一证据，我们制作了TPMRSS 13 KO小鼠，并将病毒攻击动物。在TPMRSS 13 KO小鼠中，具有血凝素（HA）切割位点序列RKKR的HPAI病毒的病毒增殖部分受到抑制，而具有序列KKKR的HPAI病毒的病毒增殖完全受到抑制。结果表明，MSPL/TMPRSS 13对于HPAI病毒的进入是必需的。此外，我们发现病毒感染会刺激流感。细胞因子蛋白酶循环在感染引起的多器官功能衰竭的致病中起重要作用。

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.