Journal article
Anti-glycoprotein H antibody impairs the pathogenicity of varicella-zoster virus in skin xenografts in the SCID mouse model
Journal of virology, Vol.84(1), pp.141-152
01/2010
DOI: 10.1128/JVI.01338-09
PMCID: PMC2798403
PMID: 19828615
Abstract
Varicella-zoster virus (VZV) infection is usually mild in healthy individuals but can cause severe disease in immunocompromised patients. Prophylaxis with varicella-zoster immunoglobulin can reduce the severity of VZV if given shortly after exposure. Glycoprotein H (gH) is a highly conserved herpesvirus protein with functions in virus entry and cell-cell spread and is a target of neutralizing antibodies. The anti-gH monoclonal antibody (MAb) 206 neutralizes VZV in vitro. To determine the requirement for gH in VZV pathogenesis in vivo, MAb 206 was administered to SCID mice with human skin xenografts inoculated with VZV. Anti-gH antibody given at 6 h postinfection significantly reduced the frequency of skin xenograft infection by 42%. Virus titers, genome copies, and lesion size were decreased in xenografts that became infected. In contrast, administering anti-gH antibody at 4 days postinfection suppressed VZV replication but did not reduce the frequency of infection. The neutralizing anti-gH MAb 206 blocked virus entry, cell fusion, or both in skin in vivo. In vitro, MAb 206 bound to plasma membranes and to surface virus particles. Antibody was internalized into vacuoles within infected cells, associated with intracellular virus particles, and colocalized with markers for early endosomes and multivesicular bodies but not the trans-Golgi network. MAb 206 blocked spread, altered intracellular trafficking of gH, and bound to surface VZV particles, which might facilitate their uptake and targeting for degradation. As a consequence, antibody interference with gH function would likely prevent or significantly reduce VZV replication in skin during primary or recurrent infection.
Details
- Title: Subtitle
- Anti-glycoprotein H antibody impairs the pathogenicity of varicella-zoster virus in skin xenografts in the SCID mouse model
- Creators
- Susan E Vleck - Stanford University, Stanford, CA 94305, USA. sevleck@stanford.eduStefan L OliverMike ReicheltJaya RajamaniLeigh ZerboniCarol JonesJames ZehnderCharles GroseAnn M Arvin
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.84(1), pp.141-152
- DOI
- 10.1128/JVI.01338-09
- PMID
- 19828615
- PMCID
- PMC2798403
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- T32 AI07328. / NIAID NIH HHS R01 AI020459 / NIAID NIH HHS P01CA49605 / NCI NIH HHS T32 GM007279 / NIGMS NIH HHS R01 AI 020459 / NIAID NIH HHS P01 CA049605 / NCI NIH HHS T32 AI007328 / NIAID NIH HHS
- Language
- English
- Date published
- 01/2010
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093230502771
Metrics
23 Record Views