To establish the therapeutic strategies for viral infections, we have studied three approaches. First, we found novel anti-viral host cellular factor. Inhibition of kinesin family member KIF18A strongly suppressed influenza viral replication by preventing the nuclear export of viral ribonucleoprotein complexes. Second, we identified the underlying mechanism for T cell-mediated immunopathogenesis upon chronic viral infections. Sphingosine kinase 2 functions during chronic viral infection to limit T cell immune pathology, which subsequently aids in the establishment of virus-induced immunosuppression and the resultant viral persistence. Third, we identified novel candidate proteins that are associated with antigen presentation by dendritic cells, which potentially promotes the development of novel vaccines to prevent viral infections. Our results provide novel insights into the treatment of acute and chronic viral infections.