JC virus enters human glial cells by clathrin-dependent receptor-mediated endocytosis

The human polyomavirus JC virus (JCV) is the etiologic agent of a fatal cen tral nervous system (CNS) demyelinating disease known as progressive multif ocal leukoencephalopathy (PML), PML occurs predominantly in immunosuppresse d patients and has increased dramatically as a result of the AIDS pandemic, The major target cell of JCV infection and lytic replication in the CNS is the oligodendrocyte, The mechanisms by which JCV initiates and establishes infection of these glial cells are not understood. The initial interaction between JCV and glial cells involves virus binding to N-linked glycoprotei ns containing terminal alpha(2-6)-linked sialic acids. The subsequent steps of entry and targeting of the viral genome to the nucleus have not been de scribed. In this report, we compare the kinetics and mechanisms of infectio us entry of JCV into human glial cells with that of the related polyomaviru s, simian virus 40 (SV40), We demonstrate that JCV, unlike SV40, enters gli al cells by receptor-mediated clathrin-dependent endocytosis.