Additionally, ZIKV can be transmitted by sexual, blood-borne and maternal-fetal routes, and male infertility has been reported in mouse and human studies. However, the outbreak of Zika virus, emerging since 2016 in French Polynesia and in South America and spreading immediately globally, was linked to Guillain–Barre syndrome in adults as well as an increase in fetal abnormalities, including placental insufficiency, microcephaly, making ZIKV infection a global health crisis by the World Health Organization. Infection with ZIKV in humans is often asymptomatic or mild, consisting of skin rashes, conjunctivitis, fever and headaches. Although human infection was reported as early as 1964, the first major ZIKV outbreak did not occur until 2007 in Yap Island, where over 70% of the population within the island became infected. Our data characterized an overall landscape of the immunogenic spectrum of the ZIKV polyprotein, and provide useful insight into the vaccine development.Īs a mosquito-borne virus belonging to the flavivirus genus of the Flaviviridae family, Zika virus (ZIKV) was firstly isolated in 1947 from rhesus macaque ( Macaca mulatta) in the Zika forest, Uganda. Through the identification of CD8+ T cell epitopes, we found that immunodominant regions E 294-302 and NS4 2351-2360 are hotspots epitopes with a distinct immunodominance hierarchy present in H-2 b and H-2 d mice, respectively. Among the synthesized 364 overlapping polypeptides spanning the whole proteome of ZIKV, we mapped 91 and 39 polypeptides which can induce ZIKV-specific T cell responses in H-2 b and H-2 d mice, respectively. In contrast, in H-2 d mice, NS1 and NS4 are the dominant CD8+ T cell antigen and NS4 as the dominant CD4+ T cell antigen, respectively. In H-2 b mice, the proteins E, NS2, NS3 and NS5 are recognized as immunodominant antigens by CD8+ T cells, while NS4 is dominantly recognized by CD4+ T cells. Herein, we have depicted the profile of CD8+ and CD4+ T cell immunogenicity of ZIKV proteins in C57BL/6 (H-2 b) and BALB/c (H-2 d) mice, and found that featured cellular immunity antigens were variant among different murine alleles. Zika virus (ZIKV)-specific T cells are activated by different peptides derived from virus structural and nonstructural proteins, and contributed to the viral clearance or protective immunity.
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