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Envelope domain III E324, E351, and E380 mutations lever adaptive evolution of DENV-1 genotype I.
Jiang, Tao; Huang, Chenxiao; Ruan, Qianqian; Huang, Xiaorong; Liang, Chumin; Chen, Zhiqiang; Yu, Xi; Peng, Yihao; Liu, Zheng; Cheng, Gong; Dai, Jianfeng; Sun, Jiufeng.
Afiliación
  • Jiang T; Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Huang C; MOE Key Laboratory of Geriatric Diseases and Immunology, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Ruan Q; Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Huang X; MOE Key Laboratory of Geriatric Diseases and Immunology, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Liang C; Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  • Chen Z; School of Public Health, Sun Yat-Sen University, Guangzhou, China.
  • Yu X; Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  • Peng Y; Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  • Liu Z; Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Cheng G; MOE Key Laboratory of Geriatric Diseases and Immunology, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Dai J; Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China.
  • Sun J; School of Medicine, Kobilka Institute of Innovative Drug Discovery, the Chinese University of Hong Kong (Shenzhen), Shenzhen, China.
J Virol ; : e0118324, 2024 Sep 04.
Article en En | MEDLINE | ID: mdl-39230303
ABSTRACT
Dengue virus (DENV) gains genetic mutations during continuous transmission and evolution, making the virus more adaptive and virulent. The clade of DENV-1 genotype I has expanded and become the predominant genotype in Asia and the Pacific areas, but the underlying mechanisms are unclear. A combined analysis of nonsynonymous mutations in domain III of the envelope protein and their biological effects on virus pathogenesis and transmission was evaluated. Phylogenetic analyses found three nonsynonymous mutations (V324I, V351L, and V380I) in domain III of the envelope protein, which emerged in 1970s-1990s and stably inherited and expanded in contemporary strains after 2000. We generated reverse-mutated viruses (I324V, L351V, and I380V) based on an infectious clone of an epidemic DENV-1 strain (NIID02-20), and the results suggested that the infectivity of the contemporary epidemic virus (wild type, WT) has increased compared to the reverse mutant viruses in mammalian hosts but not mosquito vectors. The WT virus showed a higher binding affinity to host cells and increased virion stability. In addition, weaker immunogenicity and higher resistance to neutralizing antibodies of the WT virus indicated a trend of immune escape. The data suggested that nonsynonymous mutations of the E protein (V324I, V351L, and V380I) promote infectivity and immune evasion of DENV-1 genotype I, which may facilitate its onward transmission on a global scale. IMPORTANCE We provide evidence that minor sequence variation among dengue virus (DENV) strains can result in increased adaptability and virulence, impacting both the biology of the virus and the antiviral immune response. The genetic mutations of DENV-1 gained during continuous transmission and evolution will offer new clues for the design of novel vaccines against flaviviruses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Virol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Virol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos