Please use this identifier to cite or link to this item:
https://doi.org/10.1128/mBio.02134-16
DC Field | Value | |
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dc.title | Understanding zika virus stability and developing a chimeric vaccine through functional analysis | |
dc.contributor.author | Xie, X | |
dc.contributor.author | Yang, Y | |
dc.contributor.author | Muruato, A.E | |
dc.contributor.author | Zou, J | |
dc.contributor.author | Shan, C | |
dc.contributor.author | Nunes, B.T.D | |
dc.contributor.author | Medeiros, D.B.A | |
dc.contributor.author | Vasconcelos, P.F.C | |
dc.contributor.author | Weaver, S.C | |
dc.contributor.author | Rossi, S.L | |
dc.contributor.author | Shi, P.-Y | |
dc.date.accessioned | 2020-11-17T06:41:14Z | |
dc.date.available | 2020-11-17T06:41:14Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Xie, X, Yang, Y, Muruato, A.E, Zou, J, Shan, C, Nunes, B.T.D, Medeiros, D.B.A, Vasconcelos, P.F.C, Weaver, S.C, Rossi, S.L, Shi, P.-Y (2017). Understanding zika virus stability and developing a chimeric vaccine through functional analysis. mBio 8 (1) : e02134-16. ScholarBank@NUS Repository. https://doi.org/10.1128/mBio.02134-16 | |
dc.identifier.issn | 2161-2129 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/183579 | |
dc.description.abstract | 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.IMPORTANCE Analysis of a recently observed high-resolution structure of ZIKV led to a hypothesis that its unusual stability may contribute to the associated, unique disease outcomes. Here we performed a functional analysis to demonstrate that viral prM-E genes are the main determinants for the high stability of ZIKV. The extra hydrogen-bond interaction (observed in the high-resolution structure) between ZIKV E proteins did not enhance virion stability, whereas the extended loop of E protein (CD loop in domain III) was essential for ZIKV assembly. More importantly, we found that a chimeric ZIKV with DENV-2 prM-E genes and a chimeric DENV-2 with ZIKV prM-E genes were highly attenuated in A129 mice. Mice immunized with these chimeric viruses generated robust neutralizing antibody responses and were fully protected from DENV-2 and ZIKV challenge, respectively, indicating that these chimeric viruses could be further developed as vaccine candidates. © 2017 Xie et al. | |
dc.publisher | American Society for Microbiology | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | neutralizing antibody | |
dc.subject | live vaccine | |
dc.subject | prM protein, Flavivirus | |
dc.subject | virus envelope protein | |
dc.subject | virus vaccine | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | antibody response | |
dc.subject | Article | |
dc.subject | cohort analysis | |
dc.subject | controlled study | |
dc.subject | Dengue virus 2 | |
dc.subject | hydrogen bond | |
dc.subject | limit of detection | |
dc.subject | limit of quantitation | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | prM E gene | |
dc.subject | thermostability | |
dc.subject | virus gene | |
dc.subject | virus morphology | |
dc.subject | virus pathogenesis | |
dc.subject | Zika fever | |
dc.subject | Zika virus | |
dc.subject | amino acid substitution | |
dc.subject | animal | |
dc.subject | dengue | |
dc.subject | Dengue virus | |
dc.subject | disease model | |
dc.subject | dna mutational analysis | |
dc.subject | gene deletion | |
dc.subject | genetic recombination | |
dc.subject | genetics | |
dc.subject | immunology | |
dc.subject | isolation and purification | |
dc.subject | physiology | |
dc.subject | radiation response | |
dc.subject | temperature | |
dc.subject | virulence | |
dc.subject | virus replication | |
dc.subject | Zika Virus Infection | |
dc.subject | Amino Acid Substitution | |
dc.subject | Animals | |
dc.subject | Dengue | |
dc.subject | Dengue Virus | |
dc.subject | Disease Models, Animal | |
dc.subject | DNA Mutational Analysis | |
dc.subject | Mice | |
dc.subject | Recombination, Genetic | |
dc.subject | Sequence Deletion | |
dc.subject | Temperature | |
dc.subject | Vaccines, Attenuated | |
dc.subject | Viral Envelope Proteins | |
dc.subject | Viral Vaccines | |
dc.subject | Virulence | |
dc.subject | Virus Replication | |
dc.subject | Zika Virus | |
dc.subject | Zika Virus Infection | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1128/mBio.02134-16 | |
dc.description.sourcetitle | mBio | |
dc.description.volume | 8 | |
dc.description.issue | 1 | |
dc.description.page | e02134-16 | |
dc.published.state | Published | |
Appears in Collections: | Elements Staff Publications |
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