Role of Protein Kinase C βII in Influenza Virus Entry via Late Endosomes

Abstract

ABSTRACT Many viruses take advantage of receptor-mediated endocytosis in order to enter target cells. We have utilized influenza virus and Semliki Forest virus (SFV) to define a role for protein kinase C βII (PKCβII) in endocytic trafficking. We show that specific PKC inhibitors prevent influenza virus infection, suggesting a role for classical isoforms of PKC. We also examined virus entry in cells overexpressing dominant-negative forms of PKCα and -β. Cells expressing a phosphorylation-deficient form of PKCβII (T500V), but not an equivalent mutant form of PKCα, inhibited successful influenza virus entry—with the virus accumulating in late endosomes. SFV, however, believed to enter cells from the early endosome, was unaffected by PKCβII T500V expression. We also examined the trafficking of two cellular ligands, transferrin and epidermal growth factor (EGF). PKCβII T500V expression specifically blocked EGF receptor trafficking and degradation, without affecting transferrin receptor recycling. As with influenza virus, in PKCβII kinase-dead cells, EGF receptor was trapped in a late endosome compartment. Our findings suggest that PKCβII is an important regulator of a late endosomal sorting event needed for influenza virus entry and infection.