Macedo Amanda B, Resop Rachel S, Martins Laura J, Szaniawski Matthew A, Sorensen Eric S, Spivak Adam M, Nixon Douglas F, Jones R Brad, Planelles Vicente, Bosque Alberto
1 Department of Microbiology, Immunology, and Tropical Medicine, School of Medicine and Health Sciences, George Washington University , Washington, District of Columbia.
2 Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, Utah.
AIDS Res Hum Retroviruses. 2018 Sep;34(9):769-777. doi: 10.1089/AID.2018.0098. Epub 2018 Aug 10.
Primary cell models of human immunodeficiency virus (HIV) latency have become tools to both understand the mechanisms involved in establishment of latency and test preclinical strategies toward HIV-1 cure. These models rely on infection of CD4 T cells from healthy donors. As such, these models provide an opportunity to explore the role of biological sex, age, and HIV status on establishment and reactivation of latent HIV in vitro. We have used an established primary cell model of latency based on the generation of latently infected central memory CD4 T cells with the CXCR4 strain HIV-1 to address whether these variables influence (i) HIV-1 replication, (ii) establishment of latency, and (iii) latency reversal in CD4 T cells. Our results indicate that replication of HIV-1, but not establishment of latency, is influenced by the age of female, but not male, donors. Moreover, the frequency of latently infected cells in this model is directly correlated with levels of productive infection in both male and female donors independent of age. We did not find differences in the ability of five different latency-reversing agents to reactivate latent HIV-1. Finally, we have found that this model can be generated using cells from aviremic participants. In conclusion, we have further characterized the central memory T cell model of latency regarding biological sex and age and demonstrated that this model is suitable for use with cells isolated from aviremic participants, opening the opportunity to use this primary cell model to address cure approaches, including shock and kill, in HIV-infected individuals.
人类免疫缺陷病毒（HIV）潜伏的原代细胞模型已成为理解潜伏建立所涉及机制以及测试针对HIV-1治愈的临床前策略的工具。这些模型依赖于对健康供体的CD4 T细胞进行感染。因此，这些模型提供了一个机会，来探索生物学性别、年龄和HIV状态在体外潜伏HIV的建立和重新激活中的作用。我们使用了一种基于用CXCR4株HIV-1生成潜伏感染的中枢记忆CD4 T细胞而建立的原代潜伏细胞模型，以研究这些变量是否影响（i）HIV-1复制、（ii）潜伏的建立以及（iii）CD4 T细胞中的潜伏逆转。我们的结果表明，HIV-1的复制受女性供体年龄的影响，但不受男性供体年龄的影响，而潜伏的建立不受供体年龄影响。此外，在该模型中，潜伏感染细胞的频率与男性和女性供体中 productive infection 的水平直接相关，且与年龄无关。我们没有发现五种不同的潜伏逆转剂在重新激活潜伏HIV-1的能力上存在差异。最后，我们发现该模型可以使用来自无病毒血症参与者的细胞生成。总之，我们进一步在生物学性别和年龄方面对中枢记忆T细胞潜伏模型进行了表征，并证明该模型适用于从无病毒血症参与者分离的细胞，为使用这个原代细胞模型来解决HIV感染者的治愈方法（包括“激活并杀死”）开辟了机会。 （注：原文中“productive infection”未明确准确中文释义，暂保留英文）
