Anti-Glycoprotein H Antibody Impairs the Pathogenicity of Varicella-Zoster Virus in Skin Xenografts in the SCID Mouse Model

被引:17
|
作者
Vleck, Susan E. [1 ]
Oliver, Stefan L. [1 ]
Reichelt, Mike [1 ]
Rajamani, Jaya [1 ]
Zerboni, Leigh [1 ]
Jones, Carol [2 ]
Zehnder, James [2 ]
Grose, Charles [3 ]
Arvin, Ann M. [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Pediat & Microbiol & Immunol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[3] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
基金
美国国家卫生研究院;
关键词
EPSTEIN-BARR-VIRUS; VIRAL REPLICATION; IMMUNE-RESPONSE; T-CELLS; GH-GL; NEUTRALIZING ANTIBODIES; INDUCED INTERNALIZATION; MONOCLONAL-ANTIBODIES; CYTOPLASMIC TAIL; MEMBRANE-FUSION;
D O I
10.1128/JVI.01338-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:141 / 152
页数:12
相关论文
共 50 条
  • [21] Differentiation of varicella-zoster virus ORF47 protein kinase and IE62 protein binding domains and their contributions to replication in human skin xenografts in the SCID-hu mouse
    Besser, J
    Sommer, MH
    Zerboni, L
    Bagowski, CP
    Ito, H
    Moffat, J
    Ku, CC
    Arvin, AM
    JOURNAL OF VIROLOGY, 2003, 77 (10) : 5964 - 5974
  • [22] INHIBITION OF VARICELLA-ZOSTER VIRUS (VZV) GLYCOPROTEIN EXPRESSION BY A HUMAN MONOCLONAL-ANTIBODY AGAINST VZV GLYCOPROTEIN-III
    ITO, M
    MIZUTANI, K
    KAMIYA, T
    IHARA, T
    KAMIYA, H
    SAKURAI, M
    SUGANO, T
    MATUMOTO, Y
    JOURNAL OF INFECTIOUS DISEASES, 1993, 168 (05): : 1256 - 1259
  • [23] Structure-function analysis of varicella-zoster virus glycoprotein H identifies domain-specific roles for fusion and skin tropism
    Vleck, Susan E.
    Oliver, Stefan L.
    Brady, Jennifer J.
    Blau, Helen M.
    Rajamani, Jaya
    Sommer, Marvin H.
    Arvin, Ann M.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (45) : 18412 - 18417
  • [24] Discordant varicella-zoster virus glycoprotein C expression and localization between cultured cells and human skin vesicles
    Storlie, Johnathan
    Carpenter, John E.
    Jackson, Wallen
    Grose, Charles
    VIROLOGY, 2008, 382 (02) : 171 - 181
  • [25] Immunization with Varicella-zoster virus glycoprotein E expressing vectors:: Comparison of antibody response to DNA vaccine and recombinant vaccinia virus
    Stasíková, J
    Kutinová, L
    Smahel, M
    Nemecková, S
    ACTA VIROLOGICA, 2003, 47 (01) : 1 - 10
  • [26] SENSITIVE ENZYME-LINKED-IMMUNOSORBENT-ASSAY FOR ANTIBODY TO VARICELLA-ZOSTER VIRUS USING PURIFIED VZV GLYCOPROTEIN ANTIGEN
    WASMUTH, EH
    MILLER, WJ
    JOURNAL OF MEDICAL VIROLOGY, 1990, 32 (03) : 189 - 193
  • [27] Varicella-Zoster virus pathogenesis and immunobiology: New concepts emerging from investigations with the SCIDhu mouse model
    Ku, CC
    Besser, J
    Abendroth, A
    Grose, C
    Arvin, AM
    JOURNAL OF VIROLOGY, 2005, 79 (05) : 2651 - 2658
  • [28] Development of a varicella-zoster virus neutralization assay using a glycoprotein K antibody enzyme-linked immunosorbent spot assay
    Chen, Lihong
    Liu, Jian
    Wang, Wei
    Ye, Jianghui
    Wen, Lanling
    Zhao, Qinjian
    Zhu, Hua
    Cheng, Tong
    Xia, Ningshao
    JOURNAL OF VIROLOGICAL METHODS, 2014, 200 : 10 - 14
  • [29] An immunoreceptor tyrosine-based inhibition motif in varicella-zoster virus glycoprotein B regulates cell fusion and skin pathogenesis
    Oliver, Stefan L.
    Brady, Jennifer J.
    Sommer, Marvin H.
    Reichelt, Mike
    Sung, Phillip
    Blau, Helen M.
    Arvin, Ann M.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (05) : 1911 - 1916
  • [30] Analysis of varicella zoster virus attenuation by evaluation of chimeric parent Oka/vaccine Oka recombinant viruses in skin xenografts in the SCIDhu mouse model
    Zerboni, L
    Hinchliffe, S
    Sommer, MH
    Ito, H
    Besser, J
    Stamatis, S
    Cheng, J
    DiStefano, D
    Kraiouchkine, N
    Shaw, A
    Arvin, AM
    VIROLOGY, 2005, 332 (01) : 337 - 346