Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo.
Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo.
复制标题
单细胞转录组学鉴定了体内 HIV-1 的胸腺肽α限制。
DOI：
10.1126/scitranslmed.adg0873
复制
发表时间：
2023
影响因子：
17.1
通讯作者：
Pha
中科院分区：
文献类型：
--
作者：
Geretz,Aviva;Ehrenberg,PhilipK;Clifford,RobertJ;Laliberté,Alexandre;PrelliBozzo,Caterina;Eiser,Daina;Kundu,Gautam;Yum,LaurenK;Apps,Richard;Creegan,Matthew;Gunady,Mohamed;Shangguan,Shida;Sanders-Buell,Eric;Sacdalan,Carlo;Pha
宿主限制因子在先天性抗病毒防御中起关键作用，但对它们中哪些限制HIV-1在体内仍然知之甚少。在这里，我们使用单细胞转录组学分析，以确定在急性感染过程中与HIV-1控制相关的宿主因素，通过将宿主基因表达与单个细胞内的病毒RNA丰度相关联。对一名血浆病毒载量最高的参与者的细胞进行广泛测序，结果显示细胞内病毒RNA转录与编码胸腺素α原的基因PTMA的表达呈负相关。这种关联在全基因组范围内具有显著性（P调整< 0.05），并在来自泰国和美洲的另外28名分别感染HIV-1 CRF 01_AE和亚型B的参与者中得到验证。在体外过表达胸腺素α原证实了这种细胞因子抑制HIV-1的转录和感染性病毒的产生。我们的研究结果确定了胸腺素α原作为限制体内HIV-1感染的宿主因子，这对病毒传播和治疗策略具有意义。
Host restriction factors play key roles in innate antiviral defense, but it remains poorly understood which of them restricts HIV-1 in vivo. Here, we used single-cell transcriptomic analysis to identify host factors associated with HIV-1 control during acute infection by correlating host gene expression with viral RNA abundance within individual cells. Wide sequencing of cells from one participant with the highest plasma viral load revealed that intracellular viral RNA transcription correlates inversely with expression of the genePTMA, which encodes prothymosin α. This association was genome-wide significant (Padjusted< 0.05) and was validated in 28 additional participants from Thailand and the Americas with HIV-1 CRF01_AE and subtype B infections, respectively. Overexpression of prothymosin α in vitro confirmed that this cellular factor inhibits HIV-1 transcription and infectious virus production. Our results identify prothymosin α as a host factor that restricts HIV-1 infection in vivo, which has implications for viral transmission and cure strategies.