Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection.

Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection.
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DOI:
10.1371/journal.pone.0190617
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Golos TG
Golos TG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mohr EL;Block LN;Newman CM;Stewart LM;Koenig M;Semler M;Breitbach ME;Teixeira LBC;Zeng X;Weiler AM;Barry GL;Thoong TH;Wiepz GJ;Dudley DM;Simmons HA;Mejia A;Morgan TK;Salamat MS;Kohn S;Antony KM;Aliota MT;Mohns MS;Hayes JM;Schultz-Darken N;Schotzko ML;Peterson E;Capuano S 3rd;Osorio JE;O'Connor SL;Friedrich TC;O'Connor DH;Golos TG

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先天性寨卡病毒(ZIKV)感染会影响胎儿发育和妊娠结局。我们在怀孕的前三个月用波多黎各ZIKV分离株感染了一只怀孕的恒河猴。妊娠并发早产胎膜早破(PPROM)、羊膜内细菌感染和感染后49天(妊娠95天)的胎儿死亡。母胎界面的显著病理学包括急性绒毛膜炎、胎盘梗死和子宫肌层桡动脉的白细胞破碎性血管炎。在尸检时,ZIKV RNA散布在整个胎儿组织和母体免疫系统组织中,如通过病毒RNA的定量RT-PCR所评估的。通过针对病毒复制中间体的荧光原位杂交,在胎儿组织、母体子宫和母体脾脏中鉴定复制ZIKV。胎儿眼部病理学包括脉络膜缺损、疑似眼前节发育不全和视网膜发育不良。这是恒河猴先天性ZIKV感染后母体和胎儿组织中眼部病理学和延长的病毒复制的首次报道。PPROM随后胎儿死亡和视觉系统的严重病理学先前尚未在猕猴先天性ZIKV感染中描述。虽然这种妊娠期间ZIKV感染的病例因PPROM的细菌感染而复杂化,但ZIKV对这种结果的作用无法精确定义,并且进一步的非人灵长类动物研究将确定PPROM或其他不良妊娠结果的风险增加是否与先天性ZIKV感染相关。
Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection.
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