title: Differential replication of pathogenic and nonpathogenic strains of West Nile virus within astrocytes.
abstract: The severity of West Nile virus (WNV) infection in immunocompetent animals is highly strain dependent, ranging from avirulent to highly neuropathogenic. Here, we investigate the nature of this strain-specific restriction by analyzing the replication of avirulent (WNV-MAD78) and highly virulent (WNV-NY) strains in neurons, astrocytes, and microvascular endothelial cells, which comprise the neurovascular unit within the central nervous system (CNS). We demonstrate that WNV-MAD78 replicated in and traversed brain microvascular endothelial cells as efficiently as WNV-NY. Likewise, similar levels of replication were detected in neurons. Thus, WNV-MAD78's nonneuropathogenic phenotype is not due to an intrinsic inability to replicate in key target cells within the CNS. In contrast, replication of WNV-MAD78 was delayed and reduced compared to that of WNV-NY in astrocytes. The reduced susceptibility of astrocytes to WNV-MAD78 was due to a delay in viral genome replication and an interferon-independent reduction in cell-to-cell spread. Together, our data suggest that astrocytes regulate WNV spread within the CNS and therefore are an attractive target for ameliorating WNV-induced neuropathology.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland College Park, College Park, Maryland, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Hussmann
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Samuel
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Fredericksen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000821:virology*; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000821:virology*; D006801:Humans; D055806:Microvessels / Q000166:cytology / Q000821:virology; D009474:Neurons / Q000821:virology; D014709:Vero Cells; D014779:Virus Replication; D014901:West Nile Fever / Q000635:transmission / Q000821:virology; D014902:West Nile virus / Q000502:physiology*