CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection
Summary: The underlying mechanisms by which prior immunity to dengue virus (DENV) affords cross-protection against the related flavivirus Zika virus (ZIKV) are poorly understood. Here, we examine the ability of DENV/ZIKV-cross-reactive CD4+ T cells to protect against versus exacerbate ZIKV infection...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720305155 |
| _version_ | 1819139871721127936 |
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| author | Jinsheng Wen Ying-Ting Wang Kristen M. Valentine Rúbens Prince dos Santos Alves Zhigang Xu Jose Angel Regla-Nava Annie Elong Ngono Matthew P. Young Luís C.S. Ferreira Sujan Shresta |
| author_facet | Jinsheng Wen Ying-Ting Wang Kristen M. Valentine Rúbens Prince dos Santos Alves Zhigang Xu Jose Angel Regla-Nava Annie Elong Ngono Matthew P. Young Luís C.S. Ferreira Sujan Shresta |
| author_sort | Jinsheng Wen |
| collection | DOAJ |
| description | Summary: The underlying mechanisms by which prior immunity to dengue virus (DENV) affords cross-protection against the related flavivirus Zika virus (ZIKV) are poorly understood. Here, we examine the ability of DENV/ZIKV-cross-reactive CD4+ T cells to protect against versus exacerbate ZIKV infection by using a histocompatibility leukocyte antigen (HLA)-DRB1∗0101 transgenic, interferon α/β receptor-deficient mouse model that supports robust DENV and ZIKV replication. By mapping the HLA-DRB1∗0101-restricted T cell response, we identify DENV/ZIKV-cross-reactive CD4+ T cell epitopes that stimulate interferon gamma (IFNγ) and/or tumor necrosis factor (TNF) production. Vaccination of naive HLA-DRB1∗0101 transgenic mice with these peptides induces a CD4+ T cell response sufficient to reduce tissue viral burden following ZIKV infection. Notably, this protective response requires IFNγ and/or TNF secretion but not anti-ZIKV immunoglobulin G (IgG) production. Thus, DENV/ZIKV-cross-reactive CD4+ T cells producing canonical Th1 cytokines can suppress ZIKV replication in an antibody-independent manner. These results may have important implications for increasing the efficacy and safety of DENV/ZIKV vaccines and for developing pan-flavivirus vaccines. : Wen et al. show that dengue and Zika virus cross-reactive CD4+ T cells reduce Zika viral burden in interferon α/β receptor-deficient HLA-DRB1∗0101 transgenic mice in an IFNγ- or TNF-dependent, antibody-independent manner. Keywords: dengue virus, Zika virus, CD4+, T cell, Th1, cross-protection, cross-reactive, peptide, mouse, IFNγ, TNF |
| first_indexed | 2024-12-22T11:29:33Z |
| format | Article |
| id | doaj.art-9012df71ec8d4628b9ab6b1aa53e4e28 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T11:29:33Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9012df71ec8d4628b9ab6b1aa53e4e282022-12-21T18:27:39ZengElsevierCell Reports2211-12472020-04-01314CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus InfectionJinsheng Wen0Ying-Ting Wang1Kristen M. Valentine2Rúbens Prince dos Santos Alves3Zhigang Xu4Jose Angel Regla-Nava5Annie Elong Ngono6Matthew P. Young7Luís C.S. Ferreira8Sujan Shresta9Division of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Immunology Innovation Team, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China; Corresponding authorDivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Vaccine Development Laboratory, Institute of Biomedical Sciences, University of São Paulo, São Paulo 14040-901, BrazilDivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USAVaccine Development Laboratory, Institute of Biomedical Sciences, University of São Paulo, São Paulo 14040-901, BrazilDivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Corresponding authorSummary: The underlying mechanisms by which prior immunity to dengue virus (DENV) affords cross-protection against the related flavivirus Zika virus (ZIKV) are poorly understood. Here, we examine the ability of DENV/ZIKV-cross-reactive CD4+ T cells to protect against versus exacerbate ZIKV infection by using a histocompatibility leukocyte antigen (HLA)-DRB1∗0101 transgenic, interferon α/β receptor-deficient mouse model that supports robust DENV and ZIKV replication. By mapping the HLA-DRB1∗0101-restricted T cell response, we identify DENV/ZIKV-cross-reactive CD4+ T cell epitopes that stimulate interferon gamma (IFNγ) and/or tumor necrosis factor (TNF) production. Vaccination of naive HLA-DRB1∗0101 transgenic mice with these peptides induces a CD4+ T cell response sufficient to reduce tissue viral burden following ZIKV infection. Notably, this protective response requires IFNγ and/or TNF secretion but not anti-ZIKV immunoglobulin G (IgG) production. Thus, DENV/ZIKV-cross-reactive CD4+ T cells producing canonical Th1 cytokines can suppress ZIKV replication in an antibody-independent manner. These results may have important implications for increasing the efficacy and safety of DENV/ZIKV vaccines and for developing pan-flavivirus vaccines. : Wen et al. show that dengue and Zika virus cross-reactive CD4+ T cells reduce Zika viral burden in interferon α/β receptor-deficient HLA-DRB1∗0101 transgenic mice in an IFNγ- or TNF-dependent, antibody-independent manner. Keywords: dengue virus, Zika virus, CD4+, T cell, Th1, cross-protection, cross-reactive, peptide, mouse, IFNγ, TNFhttp://www.sciencedirect.com/science/article/pii/S2211124720305155 |
| spellingShingle | Jinsheng Wen Ying-Ting Wang Kristen M. Valentine Rúbens Prince dos Santos Alves Zhigang Xu Jose Angel Regla-Nava Annie Elong Ngono Matthew P. Young Luís C.S. Ferreira Sujan Shresta CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection Cell Reports |
| title | CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection |
| title_full | CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection |
| title_fullStr | CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection |
| title_full_unstemmed | CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection |
| title_short | CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection |
| title_sort | cd4 t cells cross reactive with dengue and zika viruses protect against zika virus infection |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720305155 |
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