Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.
Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.
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DOI：
10.1016/j.cell.2018.03.019
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发表时间：
2018-05-17
期刊：
影响因子：
64.5
通讯作者：
Barouch DH
中科院分区：
文献类型：
--
作者：
Martinot AJ;Abbink P;Afacan O;Prohl AK;Bronson R;Hecht JL;Borducchi EN;Larocca RA;Peterson RL;Rinaldi W;Ferguson M;Didier PJ;Weiss D;Lewis MG;De La Barrera RA;Yang E;Warfield SK;Barouch DH
由于缺乏已建立的非人灵长类动物模型，预防先天性寨卡病毒综合征(CZS)的干预措施的发展一直受到限制。在这里，我们表明，怀孕早期感染寨卡病毒(ZIKV)的雌性恒河猴概括了人类CZS的许多特征。我们用ZIKV感染了9只妊娠猴，其中6只在怀孕早期，3只在怀孕后期，并将结果与未感染的对照组进行了比较。在妊娠早期感染的猴子中，100%(6/6)表现出长期的母体病毒血症和胎儿神经病理，包括胎儿丢失、脑体积变小，以及脑组织病理损害，包括微钙化、出血、坏死、血管炎、胶质细胞增生和神经前体细胞凋亡。高分辨率核磁共振显示一致的病变提示深部灰质损伤。我们还观察了脊椎、眼部和神经肌肉的病理变化。我们的数据显示，血管受损和神经前体细胞功能障碍是CZS发病机制的特征，提示了预防和治疗这种疾病的新策略。早孕雌性恒河猴ZIKV感染导致胎儿神经病变，血管受损，神经前体细胞功能障碍，类似于人类婴儿先天性ZIKV综合征。
The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy and 3 later in pregnancy, and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease. ZIKV infection in early pregnant female rhesus monkeys resulted in fetal neuropathology with vascular compromise and neuroprogenitor cell dysfunction, similar to congenital ZIKV syndrome in human infants.
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影响因子：
64.8
作者：
Larocca, Rafael A.;Abbink, Peter;Peron, Jean Pierre S.;Zanotto, Paolo M. de A.;Iampietro, M. Justin;Badamchi-Zadeh, Alexander;Boyd, Michael;Ng'ang'a, David;Kirilova, Marinela;Nityanandam, Ramya;Mercado, Noe B.;Li, Zhenfeng;Moseley, Edward T.;Bricault, Christine A.;Borducchi, Erica N.;Giglio, Patricia B.;Jetton, David;Neubauer, George;Nkolola, Joseph P.;Maxfield, Lori F.;De La Barrera, Rafael A.;Jarman, Richard G.;Eckels, Kenneth H.;Michael, Nelson L.;Thomas, Stephen J.;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
影响因子：
3.7
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
通讯作者：
Golos TG
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
120.7
作者：
Honein, Margaret A.;Dawson, April L.;Jamieson, Denise J.
通讯作者：
Jamieson, Denise J.
影响因子：
168.9
作者：
Adibi, Jennifer J.;Marques, Ernesto T. A., Jr.;Beigi, Richard H.
通讯作者：
Beigi, Richard H.