Your browser doesn't support javascript.
loading
LDLR is used as a cell entry receptor by multiple alphaviruses.
Zhai, Xiaofeng; Li, Xiaoling; Veit, Michael; Wang, Ningning; Wang, Yu; Merits, Andres; Jiang, Zhiwen; Qin, Yan; Zhang, Xiaoguang; Qi, Kaili; Jiao, Houqi; He, Wan-Ting; Chen, Ye; Mao, Yang; Su, Shuo.
Afiliación
  • Zhai X; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Li X; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Veit M; Institute for Virology, Center for Infection Medicine, Veterinary Faculty, Free University Berlin, Berlin, Germany.
  • Wang N; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Wang Y; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Merits A; Institute of Bioengineering, University of Tartu, Nooruse Street 1, 50411, Tartu, Estonia.
  • Jiang Z; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Qin Y; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Zhang X; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Qi K; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Jiao H; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • He WT; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Chen Y; Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
  • Mao Y; School of Pharmaceutical Sciences and National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, China. maoyang3@mail.sysu.edu.cn.
  • Su S; Academy for Advanced Interdisciplinary Studies, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. shuosu@njau.edu.cn.
Nat Commun ; 15(1): 622, 2024 Jan 20.
Article en En | MEDLINE | ID: mdl-38245515
ABSTRACT
Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Alphavirus / Alphavirus / Culicidae Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Alphavirus / Alphavirus / Culicidae Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido