Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.
Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.
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DOI：
10.1371/journal.ppat.1006537
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发表时间：
2017-07
期刊：
影响因子：
6.7
通讯作者：
Miller CJ
中科院分区：
文献类型：
--
作者：
Carroll T;Lo M;Lanteri M;Dutra J;Zarbock K;Silveira P;Rourke T;Ma ZM;Fritts L;O'Connor S;Busch M;Miller CJ
寨卡病毒 (ZIKV) 是一种通过蚊子传播的病毒，可导致受感染胎儿严重缺陷。 ZIKV 也可通过性接触传播，但性传播的相对重要性尚不清楚。为了更好地了解性传播在 ZIKV 发病机制中的作用，开发了一种非人灵长类动物 (NHP) 阴道传播模型。通过阴道接种 104-106 个噬菌斑形成单位 (PFU)，ZIKV 很容易传播给成熟的循环雌性恒河猴 (RM)。然而，需要 1–>8 次阴道接种才能建立感染的 RM 个体之间的易感性存在差异。经过广泛使用的避孕孕激素 Depoprovera 治疗后，两名最初对 8 次阴道 ZIKV 接种有抵抗力的 RM 在接种 1 次 ZIKV 后又被感染。因此，Depoprovera 似乎增强了寨卡病毒阴道传播的易感性。出乎意料的是，阴道内接种 ZIKV 后病毒复制和传播的动力学与皮下（SQ）病毒接种感染 ZIKV 的 RM 明显不同。多个研究小组报告称，接种 SQ ZIKV 后，血浆中可快速检测到 vRNA，而尿液和唾液中的 vRNA 较少见，并且在女性生殖道 (FRT) 分泌物中很少检测到。相比之下，在阴道接种的 RM 中，血浆 vRNA 延迟了几天，并且在所有 6 只动物中都发现了 FRT 中的 ZIKV 复制和 vRNA 脱落。此外，在阴道内传播后，在血浆 vRNA 之前或同时检测到从 FRT 分泌物中脱落的 ZIKV RNA，并且持续时间至少相同。因此，FRT 中的 ZIKV 复制独立于血浆 vRNA 的组织中的病毒复制，并且通常先于病毒复制。这些结果支持这样的结论：ZIKV 在阴道传播后优先在 FRT 中复制，但在 SQ 传播后则不然，并提出了与蚊子传播 ZIKV 相比，阴道 ZIKV 传播后胎儿感染和病理学增强的可能性。寨卡病毒于 2015 年传入巴西，并迅速传播到整个美洲热带地区。尽管寨卡病毒感染在成人中通常较轻，但它可能会导致发育中的胎儿出现严重的出生缺陷，因此预防怀孕或可能怀孕的妇女感染寨卡病毒至关重要。虽然寨卡病毒主要通过蚊子叮咬传播，但也可以通过性行为传播。为了了解性传播在寨卡病毒病中的作用，我们在恒河猴阴道内接种了该病毒，并监测了血液和生殖道分泌物中的病毒。 ZIKV 在血浆中检测到之前先在女性生殖道中检测到，并且女性生殖道中的复制水平并不反映身体其他部位的 ZIKV 水平。因此，寨卡病毒在阴道传播后更喜欢生殖道，这表明与蚊子传播寨卡病毒感染相比，寨卡病毒阴道传播后胎儿疾病可能更常见或更严重。
Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104–106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1–>8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and pathology after vaginal ZIKV transmission compared to a mosquito transmitted ZIKV. Zika virus was introduced to Brazil in 2015 and it rapidly spread to all of tropical America. Although Zika virus infection is usually mild in adults, it can cause severe birth defects in the developing fetus that makes it critical to prevent ZIKV infection in women who are pregnant or who could become pregnant. Although Zika virus is transmitted primarily by mosquito bite, it can also be transmitted by sex. To understand the role of sexual transmission in Zika virus disease, we inoculated rhesus monkeys intravaginally with the virus and monitored virus in blood and reproductive tract secretions. ZIKV was detected in the female reproductive tract before it was detected in plasma and replication levels in the female reproductive tract did not reflect ZIKV levels in other parts of the body. Thus ZIKV prefers the reproductive tract after vaginal transmission suggesting that fetal disease could be more common or severe after vaginal ZIKV transmission compared to a mosquito transmitted ZIKV infection.
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影响因子：
3.7
作者：
Coffey LL;Pesavento PA;Keesler RI;Singapuri A;Watanabe J;Watanabe R;Yee J;Bliss-Moreau E;Cruzen C;Christe KL;Reader JR;von Morgenland W;Gibbons AM;Allen AM;Linnen J;Gao K;Delwart E;Simmons G;Stone M;Lanteri M;Bakkour S;Busch M;Morrison J;Van Rompay KK
通讯作者：
Van Rompay KK
影响因子：
4.6
作者：
Chuang YC;Chen HR;Yeh TM
通讯作者：
Yeh TM
DOI：
10.1128/genomea.00500-14
发表时间：
2014-06-05
期刊：
Genome announcements
影响因子：
--
作者：
Baronti C;Piorkowski G;Charrel RN;Boubis L;Leparc-Goffart I;de Lamballerie X
通讯作者：
de Lamballerie X
影响因子：
33.9
作者：
Brooks, John T.;Friedman, Allison;Jamieson, Denise J.
通讯作者：
Jamieson, Denise J.
影响因子：
5.4
作者：
Arndt, U;Wennemuth, G;Bacher, M
通讯作者：
Bacher, M