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是高致病性禽流感（HPAI）病毒进入细胞的必需细胞因子。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。具有血凝素（HA）裂解位点序列RKKR的高致病性病毒在TPMRSS13 KO小鼠体内的增殖被部分抑制，KKKR序列被完全抑制。结果表明，MSPL/ TMPRSS13是高致病性禽流感病毒进入的关键基因。此外，我们发现病毒感染会刺激流感。细胞因子。蛋白酶周期及其循环在感染诱导的多器官衰竭的致病性中起重要作用。

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.