Gag p24 是组织中人类免疫缺陷病毒表达的标志物，与免疫反应相关。
Gag p24 Is a Marker of Human Immunodeficiency Virus Expression in Tissues and Correlates With Immune Response.
机构信息
Merck & Co, Inc, Kenilworth, New Jersey, USA.
Division of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA.
出版信息
J Infect Dis. 2021 Nov 16;224(9):1593-1598. doi: 10.1093/infdis/jiab121.
Abstract
We demonstrate that human immunodeficiency virus (HIV) gag p24 protein is more readily detected in gut and lymph node tissues than in blood CD4+ T cells and correlates better with CD4 count during antiretroviral therapy (ART). Gut p24 levels also measurably decline with ART in natural controllers. During ART, gut p24 expression is more strongly associated both with HIV-specific CD8+ T-cell frequency and plasma soluble CD14 levels than gut HIV RNA expression. This study supports using gag p24 as a marker of HIV expression in HIV+ tissues to study effects of viral persistence and to monitor efficacy of treatment in HIV-based clearance studies.
摘要
我们证明，人类免疫缺陷病毒（HIV） gag p24 蛋白在肠道和淋巴结组织中比在血液 CD4+T 细胞中更容易被检测到，并且在抗逆转录病毒治疗（ART）期间与 CD4 计数的相关性更好。在天然控制器中，肠道 p24 水平也随着 ART 而显著下降。在 ART 期间，肠道 p24 的表达与 HIV 特异性 CD8+T 细胞频率和血浆可溶性 CD14 水平的相关性均强于肠道 HIV RNA 表达。本研究支持使用 gag p24 作为 HIV 感染组织中 HIV 表达的标志物，以研究病毒持续存在的影响，并监测基于 HIV 的清除研究中治疗的效果。
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3
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