Moreira-Soto Andres, Carneiro Ianei de Oliveira, Fischer Carlo, Feldmann Marie, Kümmerer Beate M, Silva Nama Santos, Santos Uilton Góes, Souza Breno Frederico de Carvalho Dominguez, Liborio Fernanda de Azevedo, Valença-Montenegro Mônica Mafra, Laroque Plautino de Oliveira, da Fontoura Fernanda Rosa, Oliveira Alberto Vinicius Dantas, Drosten Christian, de Lamballerie Xavier, Franke Carlos Roberto, Drexler Jan Felix
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany.
mSphere. 2018 Jan 31;3(1). doi: 10.1128/mSphere.00523-17. eCollection 2018 Jan-Feb.
Chikungunya virus (CHIKV) and Zika virus (ZIKV) emerged in the Americas in 2013. Limited antigenic variability of CHIKV and ZIKV may restrict urban transmission cycles due to population protective immunity. In Africa, sylvatic transmission cycles involving nonhuman primates (NHP) are known for CHIKV and ZIKV, causing cyclic reemergence in humans. To evaluate whether sylvatic cycles can be expected in Latin America, we tested 207 NHP collected between 2012 and 2017 in urban and peri-urban settings in Brazil for infection with ZIKV and CHIKV. No animal tested positive for viral RNA in genus-specific and species-specific reverse transcription-PCR (RT-PCR) assays. In contrast, six animals (2.9%) from the families Atelidae, Callitrichidae, and Cebidae showed ZIKV-specific antibodies and 11 (5.3%) showed CHIKV-specific antibodies in plaque reduction neutralization tests (PRNT). Reactivity was monotypic against either ZIKV or CHIKV in all cases, opposing unspecific virucidal activity of sera. PRNT endpoint titers were low at 1:40 in all NHP, and positive specimens did not correspond to the likely dispersal route and time of introduction of both arboviruses. All antibody-positive samples were therefore tested against the NHP-associated yellow fever virus (YFV) and Mayaro virus (MAYV) and against the human-associated dengue virus (DENV) by PRNT. Two ZIKV-positive samples were simultaneously DENV positive and two CHIKV-positive samples were simultaneously MAYV positive, at titers of 1:40 to 1:160. This suggested cross-reactive antibodies against heterologous alphaviruses and flaviviruses in 24% of ZIKV-positive/CHIKV-positive sera. In sum, low seroprevalence, invariably low antibody titers, and the distribution of positive specimens call into question the capability of ZIKV and CHIKV to infect New World NHP and establish sylvatic transmission cycles. Since 2013, Zika virus (ZIKV) and chikungunya virus (CHIKV) have infected millions of people in the Americas via urban transmission cycles. Nonhuman primates (NHP) are involved in sylvatic transmission cycles maintaining ZIKV and CHIKV in the Old World. We tested NHP sampled during 2012 to 2017 in urban and peri-urban areas severely affected by ZIKV and CHIKV in Brazil. Seroprevalence and antibody titers were low for both viruses. Additionally, we found evidence for infection by heterologous viruses eliciting cross-reactive antibodies. Our data suggest that urban or peri-urban NHP are not easily infected by ZIKV and CHIKV despite intense local transmission. These data may imply that the ZIKV and CHIKV outbreaks in the Americas cannot be sustained in urban or peri-urban NHP once human population immunity limits urban transmission cycles. Investigation of diverse animals is urgently required to determine the fate of the ZIKV and CHIKV outbreaks in the Americas.
基孔肯雅病毒（CHIKV）和寨卡病毒（ZIKV）于2013年在美洲出现。由于人群保护性免疫，CHIKV和ZIKV有限的抗原变异性可能会限制城市传播周期。在非洲，已知CHIKV和ZIKV存在涉及非人灵长类动物（NHP）的丛林传播周期，导致在人类中周期性再次出现。为了评估拉丁美洲是否可能存在丛林传播周期，我们检测了2012年至2017年间在巴西城市和城郊地区收集的207只NHP是否感染ZIKV和CHIKV。在属特异性和种特异性逆转录聚合酶链反应（RT-PCR）检测中，没有动物的病毒RNA检测呈阳性。相比之下，在蚀斑减少中和试验（PRNT）中，来自蜘蛛猴科、狨科和卷尾猴科的6只动物（2.9%）显示出ZIKV特异性抗体，11只动物（5.3%）显示出CHIKV特异性抗体。在所有情况下，反应性均为针对ZIKV或CHIKV的单型反应，与血清的非特异性杀病毒活性相反。所有NHP的PRNT终点滴度均较低，为1:40，且阳性标本与两种虫媒病毒的可能传播途径和引入时间不对应。因此，所有抗体阳性样本均通过PRNT检测其针对与NHP相关的黄热病毒（YFV）和马亚罗病毒（MAYV）以及与人类相关的登革病毒（DENV）的反应。两个ZIKV阳性样本同时为DENV阳性，两个CHIKV阳性样本同时为MAYV阳性，滴度为1:40至1:160。这表明在24%的ZIKV阳性/CHIKV阳性血清中存在针对异源甲病毒和黄病毒的交叉反应性抗体。总之，血清阳性率低、抗体滴度始终较低以及阳性标本的分布情况使人质疑ZIKV和CHIKV感染新大陆NHP并建立丛林传播周期的能力。自2013年以来，寨卡病毒（ZIKV）和基孔肯雅病毒（CHIKV）已通过城市传播周期感染了美洲数百万人。非人灵长类动物（NHP）参与了在旧世界维持ZIKV和CHIKV的丛林传播周期。我们检测了2012年至2017年间在巴西受ZIKV和CHIKV严重影响的城市和城郊地区采集的NHP。两种病毒的血清阳性率和抗体滴度均较低。此外，我们发现了由异源病毒感染引发交叉反应性抗体的证据。我们的数据表明，尽管当地传播强烈，但城市或城郊的NHP不易被ZIKV和CHIKV感染。这些数据可能意味着，一旦人群免疫力限制了城市传播周期，美洲的ZIKV和CHIKV疫情在城市或城郊的NHP中无法持续。迫切需要对多种动物进行调查，以确定美洲ZIKV和CHIKV疫情的走向。
