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Journal of Virology, January 2003, p. 460-469, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.460-469.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Sara B. Sieczkarski,1 H. Alex Brown,2 and Gary R. Whittaker1*

Microbiology and Immunology,1 Molecular Medicine, Cornell University, Ithaca, New York 148532

Received 10 June 2002/ Accepted 25 September 2002

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 ßII (PKCßII) 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 PKC{alpha} and -ß. Cells expressing a phosphorylation-deficient form of PKCßII (T500V), but not an equivalent mutant form of PKC{alpha}, 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 PKCßII T500V expression. We also examined the trafficking of two cellular ligands, transferrin and epidermal growth factor (EGF). PKCßII T500V expression specifically blocked EGF receptor trafficking and degradation, without affecting transferrin receptor recycling. As with influenza virus, in PKCßII kinase-dead cells, EGF receptor was trapped in a late endosome compartment. Our findings suggest that PKCßII is an important regulator of a late endosomal sorting event needed for influenza virus entry and infection.


* Corresponding author. Mailing address: C5141 Veterinary Medical Center, Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853. Phone: (607) 253-4019. Fax: (607) 253-3384. E-mail: grw7{at}cornell.edu.


Journal of Virology, January 2003, p. 460-469, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.460-469.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.