title: Mapping and Role of the CD8+T Cell Response During Primary Zika Virus Infection in Mice.
abstract: CD8+T cells may play a dual role in protection against and pathogenesis of flaviviruses, including Zika virus (ZIKV). We evaluated the CD8+T cell response in ZIKV-infected LysMCre+IFNARfl/flC57BL/6 (H-2b) mice lacking the type I interferon receptor in a subset of myeloid cells. In total, 26 and 15 CD8+T cell-reactive peptides for ZIKV African (MR766) and Asian (FSS13025) lineage strains, respectively, were identified and validated. CD8+T cells from infected mice were polyfunctional and mediated cytotoxicity. Adoptive transfer of ZIKV-immune CD8+T cells reduced viral burdens, whereas their depletion led to higher tissue burdens, and CD8-/-mice displayed higher mortality with ZIKV infection. Collectively, these results demonstrate that CD8+T cells protect against ZIKV infection. Further, this study provides a T cell competent mouse model for investigating ZIKV-specific T cell responses.
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Elong Ngono
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Vizcarra
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Tang
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sheets
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Yunichel
authors.initials: Y
authors.lastname: Joo
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Medicine, Molecular Microbiology, Pathology, and Immunology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gorman
authors.affiliation: Department of Medicine, Molecular Microbiology, Pathology, and Immunology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Electronic address: sujan@lji.org.
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D000071244:Zika Virus / Q000276:immunology*; D000071243:Zika Virus Infection / Q000276:immunology* / Q000821:virology
chemical_list: D019138:Antibodies, Blocking; D018984:Epitopes, T-Lymphocyte; D053633:Receptor, Interferon alpha-beta
keywords: CD8(+) T cell; LysMCre(+)IFNAR(fl/fl); Zika virus; epitope; mouse model; peptide