Protective role for PAR4 in respiratory RNA virus infection

We started investigating the role of PAR4 in viral infections. We found that deficiency in PAR4 enhances low grade influenza A virus infection. However, after high dose infection PAR4 inhibition was protective. To investigate which cell-type was responsible for the observation we crossed PAR4fl/fl mice with different cre recombinase expressing mice. First, we generated mice with PAR4 deficiency in megakaryocytes/platelets (PAR4ΔPlt, PF4cre;PAR4fl/fl) and observed that platelets are involved in lung protective mechanisms during low dose infection but again contribute to lung injury after high dose infection. Currently, we are testing if platelet PAR4 has a role in lung inflammation after high and low dose of infection. Moreover, we are investigating which cell type will reproduce the observed mortality in global PAR4 deficient mice at the low dose and if PAR4 deficiency is protective after more severe IAV infection. This way we might can explain conflicting data from us and others.