Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B
Abstract Kaposi's sarcoma‐associated herpesvirus (KSHV), a member of the human γ‐herpesviruses family, exhibits extensive cellular tropism and is associated with Kaposi's sarcoma and various B‐cell malignancies. Despite its clinical significance, no effective prophylactic vaccines or speci...
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| Format: | Article |
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202502231 |
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| author | Xin‐Yan Fang Cong Sun Chu Xie Bing‐Zhen Cheng Zheng‐Zhou Lu Ge‐Xin Zhao Sen‐Fang Sui Mu‐Sheng Zeng Zheng Liu |
| author_facet | Xin‐Yan Fang Cong Sun Chu Xie Bing‐Zhen Cheng Zheng‐Zhou Lu Ge‐Xin Zhao Sen‐Fang Sui Mu‐Sheng Zeng Zheng Liu |
| author_sort | Xin‐Yan Fang |
| collection | DOAJ |
| description | Abstract Kaposi's sarcoma‐associated herpesvirus (KSHV), a member of the human γ‐herpesviruses family, exhibits extensive cellular tropism and is associated with Kaposi's sarcoma and various B‐cell malignancies. Despite its clinical significance, no effective prophylactic vaccines or specific therapeutics are currently available to prevent or treat KSHV infection. Similar to other herpesviruses, KSHV depends on the envelope glycoprotein B (gB) for host receptor recognition and membrane fusion initiation, making gB a prime target for antiviral antibody or vaccine development. In this study, the high‐resolution cryo‐electron microscopy (cryo‐EM) structure of KSHV gB is presented, revealing a unique trimeric conformation resembling the postfusion state observed in other herpesviruses. Additionally, the structure of the non‐neutralizing monoclonal antibody 2C4 bound to KSHV gB domain IV is resolved. The comparative sequence and structure analyses reveal significant homology in neutralizing epitopes between KSHV and Epstein‐Barr virus (EBV) gB, indicating a potential pathway for the development of broad‐spectrum antiviral strategies. These findings provide a foundation for a deeper understanding of KSHV's infectious mechanism and pave the way for the creation of universal interventions against the human γ‐herpesviruses. |
| format | Article |
| id | doaj-art-461f6495d2934e56bdcf706e2ae7fc97 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-461f6495d2934e56bdcf706e2ae7fc972025-08-20T03:50:58ZengWileyAdvanced Science2198-38442025-07-011227n/an/a10.1002/advs.202502231Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein BXin‐Yan Fang0Cong Sun1Chu Xie2Bing‐Zhen Cheng3Zheng‐Zhou Lu4Ge‐Xin Zhao5Sen‐Fang Sui6Mu‐Sheng Zeng7Zheng Liu8Cryo‐electron Microscopy Center Southern University of Science and Technology Shenzhen Guangdong 518055 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. ChinaCryo‐electron Microscopy Center Southern University of Science and Technology Shenzhen Guangdong 518055 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. ChinaCryo‐electron Microscopy Center Southern University of Science and Technology Shenzhen Guangdong 518055 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. ChinaCryo‐electron Microscopy Center Southern University of Science and Technology Shenzhen Guangdong 518055 ChinaAbstract Kaposi's sarcoma‐associated herpesvirus (KSHV), a member of the human γ‐herpesviruses family, exhibits extensive cellular tropism and is associated with Kaposi's sarcoma and various B‐cell malignancies. Despite its clinical significance, no effective prophylactic vaccines or specific therapeutics are currently available to prevent or treat KSHV infection. Similar to other herpesviruses, KSHV depends on the envelope glycoprotein B (gB) for host receptor recognition and membrane fusion initiation, making gB a prime target for antiviral antibody or vaccine development. In this study, the high‐resolution cryo‐electron microscopy (cryo‐EM) structure of KSHV gB is presented, revealing a unique trimeric conformation resembling the postfusion state observed in other herpesviruses. Additionally, the structure of the non‐neutralizing monoclonal antibody 2C4 bound to KSHV gB domain IV is resolved. The comparative sequence and structure analyses reveal significant homology in neutralizing epitopes between KSHV and Epstein‐Barr virus (EBV) gB, indicating a potential pathway for the development of broad‐spectrum antiviral strategies. These findings provide a foundation for a deeper understanding of KSHV's infectious mechanism and pave the way for the creation of universal interventions against the human γ‐herpesviruses.https://doi.org/10.1002/advs.202502231antibodiescryo‐electron microscopy (cryo‐EM)glycoprotein B (gB)kaposi's sarcoma‐associated herpesvirus (KSHV) |
| spellingShingle | Xin‐Yan Fang Cong Sun Chu Xie Bing‐Zhen Cheng Zheng‐Zhou Lu Ge‐Xin Zhao Sen‐Fang Sui Mu‐Sheng Zeng Zheng Liu Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B Advanced Science antibodies cryo‐electron microscopy (cryo‐EM) glycoprotein B (gB) kaposi's sarcoma‐associated herpesvirus (KSHV) |
| title | Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B |
| title_full | Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B |
| title_fullStr | Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B |
| title_full_unstemmed | Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B |
| title_short | Structure and Antigenicity of Kaposi's Sarcoma‐Associated Herpesvirus Glycoprotein B |
| title_sort | structure and antigenicity of kaposi s sarcoma associated herpesvirus glycoprotein b |
| topic | antibodies cryo‐electron microscopy (cryo‐EM) glycoprotein B (gB) kaposi's sarcoma‐associated herpesvirus (KSHV) |
| url | https://doi.org/10.1002/advs.202502231 |
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