Novel role of host protein SLC25A42 in the HIV-1 reactivation of latent HIV-1 provirus

IF 1.9 4区 医学 Q4 IMMUNOLOGY Microbiology and Immunology Pub Date : 2024-01-20 DOI:10.1111/1348-0421.13114
Kei Taga, Hiroaki Takeuchi
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Abstract

Despite the effectiveness of combination antiretroviral therapy, human immunodeficiency virus (HIV) infection remains incurable. To seek new strategies to overcome HIV type 1 (HIV-1) latency, one of the major barriers to HIV elimination, it is crucial to better understand how this state is maintained. Here, by means of an RNA interference screen employing an HIV-1 latency model using monocytic cell lines, we identified solute carrier family 25 member 42 (SLC25A42) as a potential host factor not previously known to affect HIV-1 latency. SLC25A42 knockdown resulted in increased HIV-1 expression, whereas forced expression of exogenous SLC25A42 suppressed it in SLC25A42-depleted cells. SLC25A42 depletion increased HIV-1 proviral transcriptional elongation but did not cause HIV-1 activation in an HIV-1 Tat-depleted latency model. This suggests that the role of SLC25A42 in HIV-1 transcription depends on HIV-1 Tat. Chromatin immunoprecipitation-qPCR analysis further revealed that SLC25A42 accumulated on or near the HIV-1 5ʹ long terminal repeat promoter region of the HIV-1 provirus, suggesting a possible role in regulating HIV-1 Tat near this promoter region. These results indicate that SLC25A42 plays a novel role in HIV-1 latency maintenance in monocytic HIV-1 reservoirs.

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宿主蛋白 SLC25A42 在潜伏 HIV-1 病毒重新激活过程中的新作用。
尽管抗逆转录病毒联合疗法很有效,但人类免疫缺陷病毒(HIV)感染仍然无法治愈。要寻求新策略来克服艾滋病毒 1 型(HIV-1)潜伏期--消除艾滋病毒的主要障碍之一--就必须更好地了解这种状态是如何维持的。在这里,我们通过使用单核细胞系的 HIV-1 潜伏期模型进行 RNA 干扰筛选,发现溶质运载家族 25 成员 42(SLC25A42)是一种潜在的宿主因子,而此前并不知道它影响 HIV-1 潜伏期。敲除 SLC25A42 会导致 HIV-1 表达增加,而强制表达外源 SLC25A42 则会抑制 SLC25A42 贫化细胞中 HIV-1 的表达。在HIV-1 Tat缺失潜伏期模型中,SLC25A42缺失增加了HIV-1病毒的转录伸长,但并没有导致HIV-1激活。这表明 SLC25A42 在 HIV-1 转录中的作用取决于 HIV-1 Tat。染色质免疫沉淀-qPCR分析进一步显示,SLC25A42在HIV-1前病毒的HIV-1 5'长末端重复启动子区域或其附近积累,这表明SLC25A42可能在该启动子区域附近调节HIV-1 Tat。这些结果表明,SLC25A42在单核细胞HIV-1储库的HIV-1潜伏维持过程中发挥着新的作用。
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来源期刊
Microbiology and Immunology
Microbiology and Immunology 医学-免疫学
CiteScore
5.20
自引率
3.80%
发文量
78
审稿时长
1 months
期刊介绍: Microbiology and Immunology is published in association with Japanese Society for Bacteriology, Japanese Society for Virology, and Japanese Society for Host Defense Research. It is peer-reviewed publication that provides insight into the study of microbes and the host immune, biological and physiological responses. Fields covered by Microbiology and Immunology include:Bacteriology|Virology|Immunology|pathogenic infections in human, animals and plants|pathogenicity and virulence factors such as microbial toxins and cell-surface components|factors involved in host defense, inflammation, development of vaccines|antimicrobial agents and drug resistance of microbes|genomics and proteomics.
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