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HIV 储库:建模、定量分析和治愈方法。

HIV Reservoirs: Modeling, Quantification, and Approaches to a Cure.

机构信息

Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

Methods Mol Biol. 2022;2407:215-228. doi: 10.1007/978-1-0716-1871-4_16.

DOI:10.1007/978-1-0716-1871-4_16
PMID:34985668
Abstract

Biomedical research in animal models depends heavily on nonhuman primates (NHP) (Phillips et al., Am J Primatol 76(9):801-827, 2014). In their physiology, neurobiology, and, most importantly, their susceptibility to infectious diseases and subsequent immune responses, NHPs have many parallels with humans (Rhesus Macaque Genome Sequencing and Analysis Consortium et al., Science 316(5822):222-234, 2007). Different species of NHPs have served as important animal models for numerous infectious diseases spanning a wide range of pathogens (Gardner and Luciw, ILAR J 49(2):220-255, 2008). As a result of recognizing their utility in HIV research, NHPs have contributed to groundbreaking studies of disease pathogenesis, vaccination, and curative research (London et al., Lancet 2(8355):869-873, 1983; Henrickson et al., Lancet 1 (8321):388-390, 1983). Many African NHPs are considered natural hosts for SIV in which SIV infection is usually nonprogressive and does not cause acquired immunodeficiency syndrome (AIDS) (Chahroudi et al., Science 335(6073):1188-1193, 2012; Taaffe et al., J Virol 84(11):5476-5484, 2010). However, cross-species transmission of SIV strains to other NHPs or to humans (nonnatural hosts) leads to progressive disease and AIDS (Paiardini et al., Annu Rev Med 60:485-495, 2009). In particular, SIV infection of Asian rhesus macaques recapitulates many features of HIV infection in humans and therefore has become a widely used approach for contemporary HIV research into virus persistence and cure strategies (Gardner and Luciw, FASEB J 3(14):2593-2606, 1989). There are multiple factors that should be considered in HIV/SIV studies using NHPs including the particular monkey species and geographic background, age and sex, certain genetic properties, virus strain, route and dose of infection, interventional treatments, and prespecified study outcomes. Here, we discuss consideration of these factors to address specific questions in HIV cure research.

摘要

动物模型中的生物医学研究严重依赖于非人类灵长类动物(NHP)(Phillips 等人,Am J Primatol 76(9):801-827, 2014)。在生理学、神经生物学方面,最重要的是,它们对传染病的易感性和随后的免疫反应方面,NHP 与人类有许多相似之处(恒河猴基因组测序和分析联盟等人,Science 316(5822):222-234, 2007)。不同种类的 NHP 已成为多种传染病的重要动物模型,涵盖了广泛的病原体(Gardner 和 Luciw, ILAR J 49(2):220-255, 2008)。由于认识到它们在 HIV 研究中的效用,NHP 为疾病发病机制、疫苗接种和治疗性研究的开创性研究做出了贡献(London 等人,Lancet 2(8355):869-873, 1983;Henrickson 等人,Lancet 1 (8321):388-390, 1983)。许多非洲 NHP 被认为是 SIV 的天然宿主,在这些宿主中,SIV 感染通常是非进行性的,不会导致获得性免疫缺陷综合征(AIDS)(Chahroudi 等人,Science 335(6073):1188-1193, 2012;Taaffe 等人,J Virol 84(11):5476-5484, 2010)。然而,SIV 株从一种 NHP 物种传播到另一种 NHP 或人类(非天然宿主)会导致进行性疾病和 AIDS(Paiardini 等人,Annu Rev Med 60:485-495, 2009)。特别是,SIV 感染亚洲恒河猴再现了 HIV 感染在人类中的许多特征,因此已成为当代 HIV 研究中病毒持久性和治疗策略的广泛应用方法(Gardner 和 Luciw, FASEB J 3(14):2593-2606, 1989)。在使用 NHP 进行 HIV/SIV 研究时,有多个因素需要考虑,包括特定的猴子物种和地理背景、年龄和性别、某些遗传特性、病毒株、感染途径和剂量、干预治疗以及预设的研究结果。在这里,我们讨论了这些因素的考虑,以解决 HIV 治愈研究中的具体问题。

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