Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
Nat Commun. 2024 Nov 10;15(1):9728. doi: 10.1038/s41467-024-54146-9.
During the recent yellow fever (YF) epidemics in Brazil, human cases were attributed to spillover infections via sylvatic mosquito transmission. Despite YF virus (YFV) transmission in major urban centers with insufficient vaccination coverage and abundant populations of the domestic vector, Aedes aegypti, there was no evidence of human-amplified transmission. Furthermore, the historic absence of YF in Asia, despite abundant Ae. aegypti and an immunologically naive human population, is unexplained. We tested the hypothesis that pre-existing, heterologous flavivirus immunity, specifically from dengue (DENV) and Zika (ZIKV) viruses, limits YFV viremia and transmission by Ae. aegypti. We infected cynomolgus macaques with DENV or ZIKV, then challenged them 6-9 months later with YFV. We then measured viremia and disease and allowed Ae. aegypti mosquitoes to feed during peak macaque viremia. Although prior heterologous immunity had variable effects on disease, DENV and ZIKV immunity consistently suppressed YFV viremia. Despite no statistical difference due to a small sample size, the suppression in viremia led to a significant reduction in Ae. aegypti infection and a lack of transmission potential. These results support the hypothesis that, in DENV- and ZIKV-endemic regions such as South America and Asia, human flavivirus immunity suppresses YFV human amplification potential, reducing the risk of urban outbreaks.
在巴西最近的黄热病（YF）疫情中，人类病例归因于通过森林传播媒介的蚊种传播的溢出感染。尽管在疫苗接种覆盖率不足且国内传播媒介埃及伊蚊数量众多的主要城市中心存在 YFV 传播，但没有证据表明存在人类放大传播。此外，尽管亚洲存在大量埃及伊蚊和免疫功能尚未成熟的人群，但历史上没有 YF 的存在也无法解释。我们检验了以下假设，即预先存在的、异源黄病毒免疫，特别是来自登革热（DENV）和寨卡（ZIKV）病毒的免疫，限制了埃及伊蚊传播 YFV 的病毒血症和传播。我们用 DENV 或 ZIKV 感染食蟹猴，然后在 6-9 个月后用 YFV 进行挑战。然后，我们测量了病毒血症和疾病，并在猕猴病毒血症高峰期允许埃及伊蚊吸血。尽管先前的异源免疫对疾病有不同的影响，但 DENV 和 ZIKV 免疫始终抑制了 YFV 的病毒血症。由于样本量小，统计上没有差异，但病毒血症的抑制导致埃及伊蚊感染的显著减少和缺乏传播潜力。这些结果支持了以下假设，即在 DENV 和 ZIKV 流行地区，如南美洲和亚洲，人类黄病毒免疫抑制了 YFV 的人类放大潜力，降低了城市暴发的风险。
