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Dengue virus-reactive CD8⁺ T cells mediate cross-protection against subsequent Zika virus challenge.

ABSTRACT: Zika virus (ZIKV) and dengue virus (DENV) are antigenically related flaviviruses that share cross-reactivity in antibody and T cell responses, and co-circulate in increasing numbers of countries. Whether pre-existing DENV immunity can cross-protect or enhance ZIKV infection during sequential infection of the same host is unknown. Here, we show that DENV-immune Ifnar1 ^-/- or wild-type C57BL/6 mice infected with ZIKV have cross-reactive immunity to subsequent ZIKV infection and pathogenesis. Adoptive transfer and cell depletion studies demonstrate that DENV-immune CD8⁺ T cells predominantly mediate cross-protective responses to ZIKV. In contrast, passive transfer studies suggest that DENV-immune serum does not protect against ZIKV infection. Thus, CD8⁺ T cell immunity generated during primary DENV infection can confer protection against secondary ZIKV infection in mice. Further optimization of current DENV vaccines for T cell responses might confer cross-protection and prevent antibody-mediated enhancement of ZIKV infection.

SUBMITTER: Wen J

PROVIDER: S-EPMC5682281 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Dengue virus-reactive CD8<sup>+</sup> T cells mediate cross-protection against subsequent Zika virus challenge.

Wen Jinsheng J Elong Ngono Annie A Regla-Nava Jose Angel JA Kim Kenneth K Gorman Matthew J MJ Diamond Michael S MS Shresta Sujan S

Nature communications 20171113 1

Zika virus (ZIKV) and dengue virus (DENV) are antigenically related flaviviruses that share cross-reactivity in antibody and T cell responses, and co-circulate in increasing numbers of countries. Whether pre-existing DENV immunity can cross-protect or enhance ZIKV infection during sequential infection of the same host is unknown. Here, we show that DENV-immune Ifnar1 <sup>-/-</sup> or wild-type C57BL/6 mice infected with ZIKV have cross-reactive immunity to subsequent ZIKV infection and pathogen ...[more]

PMID: 29129917

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Project description:BackgroundZika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV.Methodology/principal findingsUsing our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form.Conclusions/significanceAn effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection, i.e., any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains.

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Dengue virus-reactive CD8⁺ T cells mediate cross-protection against subsequent Zika virus challenge.

Publications

Dengue virus-reactive CD8<sup>+</sup> T cells mediate cross-protection against subsequent Zika virus challenge.

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Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge.

Publications

Dengue virus-reactive CD8<sup>+</sup> T cells mediate cross-protection against subsequent Zika virus challenge.

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OmicsDI is part of the ELIXIR infrastructure

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Dengue virus-reactive CD8⁺ T cells mediate cross-protection against subsequent Zika virus challenge.