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用无细胞猴免疫缺陷病毒对新生恒河猴进行黏膜感染。

Mucosal infection of neonatal rhesus monkeys with cell-free SIV.

作者信息

Baba T W, Koch J, Mittler E S, Greene M, Wyand M, Penninck D, Ruprecht R M

机构信息

Laboratory of Viral Pathogenesis, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

出版信息

AIDS Res Hum Retroviruses. 1994 Apr;10(4):351-7. doi: 10.1089/aid.1994.10.351.

Abstract

Although the mechanisms for maternal transmission are unknown, approximately half of the infants congenitally infected with the human immunodeficiency virus type 1 (HIV-1) seem to become infected late in gestation or during delivery. Previously, we have developed a rhesus monkey model for congenital infection by injecting cell-free simian immunodeficiency virus (SIV) directly into amniotic fluid. Our results suggested that fetal infection may have occurred via skin or mucous membrane exposure. Mucosal surfaces have also been implicated as a portal of virus entry by a study in which the presence of serosanguinous fluid in neonatal gastric aspirates correlated with an increased rate of HIV-1 transmission. To test whether cell-free virus could transverse intact neonatal mucosal surfaces, we administered SIVmac251 orally to four rhesus monkey neonates within 1 hr following cesarean section delivery. All four neonates developed viremia and were positive by cocultivation and PCR. Seroconversion occurred in three of the four neonates. The SIV dose given was within physiological range as shown by end-point dilution of virus stock and viremic plasma samples of juvenile rhesus monkeys. This primate model for mucosal transmission of cell-free virus features a high infection rate, thus making studies of mucosal immunity and the development of strategies to prevent intrapartum virus transmission possible.

摘要

虽然母婴传播的机制尚不清楚,但约一半先天性感染1型人类免疫缺陷病毒(HIV-1)的婴儿似乎是在妊娠晚期或分娩期间被感染的。此前,我们通过将无细胞猿猴免疫缺陷病毒(SIV)直接注入羊水,建立了先天性感染的恒河猴模型。我们的结果表明,胎儿感染可能是通过皮肤或黏膜接触发生的。一项研究也表明黏膜表面可能是病毒进入的门户,该研究发现新生儿胃吸出物中血性液体的存在与HIV-1传播率的增加相关。为了测试无细胞病毒是否能穿过完整的新生儿黏膜表面,我们在剖宫产分娩后1小时内给4只恒河猴新生儿口服SIVmac251。所有4只新生儿均出现病毒血症,通过共培养和PCR检测呈阳性。4只新生儿中有3只发生了血清转化。如通过幼年恒河猴病毒储备液和病毒血症血浆样本的终点稀释所示,给予的SIV剂量在生理范围内。这种无细胞病毒黏膜传播的灵长类动物模型具有高感染率,从而使得黏膜免疫研究以及预防分娩期间病毒传播策略的开发成为可能。

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