Author(s):
Xie, Xuping ; Yang, Yujiao ; Muruato, Antonio E ; Zou, Jing ; Shan, Chao ; Nunes, Bruno Tardelli Diniz ; Medeiros, Daniele Barbosa de Almeida ; Vasconcelos, Pedro Fernando da Costa ; Weaver, Scott C ; Rossi, Shannan L ; Shia, Pei-Yong
Date: 2017
Origin: Oasisbr
Subject(s): Zika virus / gen?tica; Zika virus / fisiologia; Zika virus / efeitos de radia??o; Zika virus / imunologia; V?rus da Dengue / gen?tica; V?rus da Dengue / fisiologia; V?rus da Dengue / imunologia; V?rus da Dengue / efeitos de radia??o; Prote?nas do Envelope Viral / gen?tica; Replica??o Viral / efeitos de radia??o; An?lise Mutacional de DNA; Substitui??o de Amino?cidos; Recombina??o Gen?tica; Vacinas Atenuadas; Virul?ncia; Temperatura Ambiente; Rea??o em Cadeia da Polimerase Via Transcriptase Reversa / m?todos; Microscopia de Fluoresc?ncia / m?todos
Description
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA.
USA / Southwest University. College of Animal Science and Technology. Chongqing, China.
University of Texas Medical Branch. Institute for Human Infections and Immunity. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
University of Texas Medical Branch. Institute for Human Infections and Immunity. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA / University of Texas Medical Branch. Department of Microbiology and Immunology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA / University of Texas Medical Branch. Center for Biodefense and Emerging Infectious Diseases. Galveston, TX, USA.
University of Texas Medical Branch. Institute for Human Infections and Immunity. Galveston, TX, USA / University of Texas Medical Branch. Center for Biodefense and Emerging Infectious Diseases. Galveston, TX, USA / University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA / University of Texas Medical Branch. Department of Pharmacology & Toxicology. Galveston, TX, USA.
Compared with other flaviviruses, Zika virus (ZIKV) is uniquely associated with congenital diseases in pregnant women. One recent study reported that (i) ZIKV has higher thermostability than dengue virus (DENV [a flavivirus closely related to ZIKV]), which might contribute to the disease outcome; (ii) the higher thermostability of ZIKV could arise from an extended loop structure in domain III of the viral envelope (E) protein and an extra hydrogen-bond interaction between E molecules (V. A. Kostyuchenko, E. X. Y. Lim, S. Zhang, G. Fibriansah, T.-S. Ng, J. S. G. Ooi, J. Shi, and S.-M. Lok, Nature 533:425- 428, 2016, https://doi.org/10.1038/nature17994). Here we report the functional analysis of the structural information in the context of complete ZIKV and DENV-2 virions. Swapping the prM-E genes between ZIKV and DENV-2 switched the thermostability of the chimeric viruses, identifying the prM-E proteins as the major determinants for virion thermostability. Shortening the extended loop of the E protein by 1 amino acid was lethal for ZIKV assembly/release. Mutations (Q350I and T351V) that abolished the extra hydrogen-bond interaction between the E proteins did not reduce ZIKV thermostability, indicating that the extra interaction does not increase the thermostability. Interestingly, mutant T351V was attenuated in A129 mice defective in type I interferon receptors, even though the virus retained the wild-type thermostability. Furthermore, we found that a chimeric ZIKV with the DENV-2 prM-E and a chimeric DENV-2 with the ZIKV prM-E were highly attenuated in A129 mice; these chimeric viruses were highly immunogenic and protective against DENV-2 and ZIKV challenge, respectively. These results indicate the potential of these chimeric viruses for vaccine development.
