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Journal of Virology, January 2003, p. 1347-1356, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1347-1356.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Contrasting Roles of Endosomal pH and the Cytoskeleton in Infection of Human Glial Cells by JC Virus and Simian Virus 40

Aarthi Ashok1 and Walter J. Atwood1,2*

Department of Molecular Microbiology and Immunology,1 Graduate Program in Molecular and Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 029122

Received 5 August 2002/ Accepted 14 October 2002

Infection of eukaryotic cells by pathogens requires the efficient use of host cell endocytic and cytoplasmic transport mechanisms. Understanding how these cellular functions are exploited by microorganisms allows us to better define the basic biology of pathogenesis while providing better insight into normal cellular functions. In this report we compare and contrast intracellular transport and trafficking of the human polyomavirus JC virus (JCV) with that of simian virus 40 (SV40). We have previously shown that infection of human glial cells by JCV requires clathrin-dependent endocytosis. In contrast, infection of cells by SV40 proceeds by caveola-dependent endocytosis. We now examine the roles of endosomal pH and the cellular cytoskeleton during infection of glial cells by both viruses. Our results demonstrate that JCV infection is sensitive to disruption of endosomal pH, whereas SV40 infection is pH independent. Infection by JCV is inhibited by treatment of glial cells with cytochalasin D, nocodazole, and acrylamide, whereas SV40 infection is affected only by nocodazole. These data point to critical differences between JCV and SV40 in terms of endocytosis and intracellular trafficking of their DNA genomes to the nucleus. These data also suggest a unique sequential involvement of cytoskeletal elements during infection of glial cells by JCV.


* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Brown University, Box G-B616, 171 Meeting St., Providence, RI 02912. Phone: (401) 863-3116. Fax: (401) 863-1971. E-mail: Walter_Atwood{at}Brown.edu.


Journal of Virology, January 2003, p. 1347-1356, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1347-1356.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.