Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa

• Published in: Journal of virology 2018-04, Vol.92 (7)
• Main Authors: Herrera, Bobby Brooke, Tsai, Wen-Yang, Chang, Charlotte A, Hamel, Donald J, Wang, Wei-Kung, Lu, Yichen, Mboup, Souleymane, Kanki, Phyllis J
• Format: Article
• Language: English
• Subjects: Africa, Western - epidemiology; Cross Reactions; Dengue - diagnosis; Dengue - epidemiology; Dengue - immunology; Dengue Virus - immunology; Enzyme-Linked Immunospot Assay; Female; Humans; Pathogenesis and Immunity; RNA Helicases - immunology; Serine Endopeptidases - immunology; Viral Nonstructural Proteins - immunology; Zika Virus - immunology; Zika Virus Infection - diagnosis; Zika Virus Infection - epidemiology; Zika Virus Infection - immunology
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.01992-17

Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses. The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.