| First Author | Wen J | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 4 | Pages | 107566 |
| PubMed ID | 32348763 | Mgi Jnum | J:300584 |
| Mgi Id | MGI:6489088 | Doi | 10.1016/j.celrep.2020.107566 |
| Citation | Wen J, et al. (2020) CD4(+) T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection. Cell Rep 31(4):107566 |
| abstractText | 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 alpha/beta 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 (IFNgamma) 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 IFNgamma 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. |
