Analysis of replication mechanisms of acute respiratory viruses in epithelia

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Our studies revealed that canine distemper virus (CDV) use nectin-4 to enter epithelial and neural cells. Recently CDV has caused lethal outbreaks in monkeys. Our studies revealed that CDV has the ability to use monkey receptors as well as dog receptors. In addition, it became able to use human receptors, when it acquired a single amino acid substitution in the H protein. Also our studies showed that CDV intrinsically has the ability to counteract the human innate immune system.We have generated TMPRSS2 kockout mice. In the mice, cleavage of influenza virus HA protein was severely restricted. These data show that TMPRSS2 is the essential protease that activates influenza virus in vivo.