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.
机构:
Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Chen, Lihong
Liu, Jian
论文数: 0引用数: 0
h-index: 0
机构:
Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Liu, Jian
Wang, Wei
论文数: 0引用数: 0
h-index: 0
机构:
Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Wang, Wei
Ye, Jianghui
论文数: 0引用数: 0
h-index: 0
机构:
Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Sch Publ Hlth, Xiamen 361102, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Ye, Jianghui
Wen, Lanling
论文数: 0引用数: 0
h-index: 0
机构:
Xiamen Univ, Affiliated Zhongshan Hosp, Dept Obstet & Gynecol, Xiamen 361004, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Wen, Lanling
Zhao, Qinjian
论文数: 0引用数: 0
h-index: 0
机构:
Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Sch Publ Hlth, Xiamen 361102, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Zhao, Qinjian
Zhu, Hua
论文数: 0引用数: 0
h-index: 0
机构:
Rutgers State Univ, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ USAXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Zhu, Hua
Cheng, Tong
论文数: 0引用数: 0
h-index: 0
机构:
Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Sch Publ Hlth, Xiamen 361102, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Cheng, Tong
Xia, Ningshao
论文数: 0引用数: 0
h-index: 0
机构:
Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China
Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Sch Publ Hlth, Xiamen 361102, Fujian Province, Peoples R ChinaXiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Life Sci, Xiamen 361102, Fujian Province, Peoples R China