Broad distribution of the JC virus receptor contrasts with a marked cellular restriction of virus replication

To investigate the early events of JC virus (JCV) infection, including atta chment, penetration, transport to the nuclei, and replication of the virus, we analyzed the susceptibility of 15 different cell lines to infection usi ng a semiquantitative polymerase chain reaction (PCR) assay, in situ hybrid ization, laser scanning confocal microscopy, and a viral replication assay. The cell lines examined were human permissive and nonpermissive cells as w ell as cells of monkey and mouse origin. JCV entry into the nuclei of the a ll cell lines was observed within 10 min after inoculation, demonstrating t hat the virus receptor is widely distributed among mammalian cells. inhibit ion of viral entry by an anti-JCV VP1 antibody and sialidase treatment to r emove sialic acid residues, which are considered a candidate for the JCV re ceptor, suggested that VP1 may interact with the cellular surface sialic ac id. In addition, chlorpromazine, a clathrin-dependent pathway inhibitor, si gnificantly suppressed entry of JCV into nuclei. In spite of the broad spec trum of cells susceptible to JCV entry, replication of the virus occurred e xclusively in human neuroblastoma cell lines. These results suggest that wh ereas JCV can enter a wide variety of cell types and localize to the nuclei , cell-specific intranuclear mechanisms are required for virus replication. (C) 2001 Academic Press.