Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis.
The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which migrate to the draining lymph node following activation. A point mutation in the E2 glycoprotein gene of VEE that renders the virus avirulent and compromises its ability to spread beyond the draining lymph blocked the appearance of virally infected dendritic cells in the lymph node in vivo. A second-site suppressor mutation that restores viral spread to lymphoid tissues and partially restore virulence likewise restored the ability of VEE to infect dendritic cells in vivo.
MacDonald
G H
GH
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599-7290, USA. gmacd@med.unc.edu
Johnston
R E
RE
D000818:Animals; D002460:Cell Line; D005591:Chemical Fractionation; D006224:Cricetinae; D003713:Dendritic Cells / Q000821:virology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000472:pathogenicity*; D004685:Encephalomyelitis, Venezuelan Equine / Q000473:pathology / Q000821:virology; D049452:Green Fluorescent Proteins; D007279:Injections, Subcutaneous; D007801:Langerhans Cells / Q000821:virology; D008164:Luminescent Proteins; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology
D008164:Luminescent Proteins; D014759:Viral Envelope Proteins; C064956:glycoprotein E2, equine encephalitis virus; D049452:Green Fluorescent Proteins