title: Mechanism of lymphocytic choriomeningitis virus entry into cells.
abstract: The path that the arenavirus lymphocytic choriomeningitis virus (LCMV) uses to enter rodent fibroblastic cell lines was dissected by infectivity and inhibition studies and immunoelectron microscopy. Lysosomotropic weak bases (chloroquine and ammonium chloride) and carboxylic ionophores (monensin and nigericin) inhibited virus entry, assessed as virus nucleoprotein expression at early times post-infection, indicating that the entry process involved a pH-dependent fusion step in intracellular vesicles. That entry occurred in vesicles rather than by direct fusion of virions with the plasma membrane was confirmed by immunoelectron microscopy. The vesicles involved were large (150-300 nm diameter), smooth-walled, and not associated with clathrin. Unlike classical phagocytosis, virus uptake in these vesicles was a microfilament-independent process, as it was not blocked by cytochalasins. LCMV entry into rodent fibroblast cell lines thus involves viropexis in large smooth-walled vesicles, followed by a pH-dependent fusion event inside the cell.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
authors.forename: P
authors.initials: P
authors.lastname: Borrow
authors.forename: M B
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000468:Alkalies / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000382:microbiology; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D006863:Hydrogen-Ion Concentration; D008216:Lymphocytic Choriomeningitis / Q000382:microbiology; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000472:pathogenicity* / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D011991:Receptors, Virus / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000468:Alkalies; D000998:Antiviral Agents; D011991:Receptors, Virus