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幼年猕猴经口感染猴免疫缺陷病毒后的早期病毒复制位点:对发病机制的影响

Early Sites of Virus Replication After Oral SIV Infection of Infant Macaques: Implications for Pathogenesis.

作者信息

Amedee Angela M, Phillips Bonnie, Jensen Kara, Robichaux Spencer, Lacour Nedra, Burke Mark, Piatak Michael, Lifson Jeffrey D, Kozlowski Pamela A, Van Rompay Koen K A, De Paris Kristina

机构信息

1 Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center , New Orleans, Louisiana.

2 Department of Microbiology and Immunology and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.

出版信息

AIDS Res Hum Retroviruses. 2018 Mar;34(3):286-299. doi: 10.1089/AID.2017.0169. Epub 2018 Jan 17.

DOI:10.1089/AID.2017.0169
PMID:29237287
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5863100/
Abstract

Despite optimization of preventative measures for vertical HIV-1 transmission, daily, roughly 400 infants become HIV infected, most of them through breastfeeding. Viral entry has been presumed to occur in the gastrointestinal tract; however, the exact entry site(s) have not been defined. Therefore, we quantified simian immunodeficiency virus (SIV) RNA and DNA in oral, intestinal, and systemic tissues of 15 infant macaques within 48-96 h after oral SIV exposure. SIV DNA was detected as early as 48 h, whereas SIV RNA was typically detected at later time points (72-96 h). Transmitted founder viruses were identical or very similar to a single genotype in the SIV challenge stock. SIV RNA and DNA were most frequently found in lymph nodes (LNs) draining the oral cavity and in the ileum. Using in situ hybridization, SIV-infected cells in LNs were exclusively represented by CD3 T cells. SIV RNA and DNA were also detected in the lungs of 20% of the animals, and 60% of the animals had detectable SIV DNA in the cerebrum. The early detection of viral RNA or DNA in lung and brain tissues emphasizes the need for early treatment of pediatric HIV infection to prevent damage not only to the immune system but also to the respiratory tract and central nervous system.

摘要

尽管针对HIV-1垂直传播的预防措施已得到优化,但每天仍约有400名婴儿感染HIV,其中大多数是通过母乳喂养感染的。病毒进入被推测发生在胃肠道;然而,确切的进入部位尚未确定。因此,我们在15只婴猴口服SIV后48 - 96小时内,对其口腔、肠道和全身组织中的猿猴免疫缺陷病毒(SIV)RNA和DNA进行了定量分析。SIV DNA最早在48小时被检测到,而SIV RNA通常在较晚的时间点(72 - 96小时)被检测到。传播的奠基病毒与SIV攻击储备中的单一基因型相同或非常相似。SIV RNA和DNA最常出现在引流口腔的淋巴结(LN)和回肠中。使用原位杂交技术,LN中被SIV感染的细胞仅由CD3 T细胞代表。20%的动物肺部也检测到了SIV RNA和DNA,60%的动物大脑中检测到了可检测到的SIV DNA。在肺和脑组织中早期检测到病毒RNA或DNA强调了对儿科HIV感染进行早期治疗的必要性,以防止不仅对免疫系统,而且对呼吸道和中枢神经系统造成损害。

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