在未接受治疗和接受抗逆转录病毒治疗的个体中检测HIV-1反义转录本。
detection of HIV-1 antisense transcripts in untreated and ART-treated individuals.
作者信息
Capoferri Adam A, Sklutuis Rachel, Famuyiwa Toluleke O, Pathak Sachi, Li Rui, Rausch Jason W, Luke Brian T, Hoh Rebecca, Deeks Steven G, Mellors John W, Coffin John M, Groebner Jennifer L, Romerio Fabio, Kearney Mary F
机构信息
HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD, USA.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
bioRxiv. 2025 Feb 25:2024.12.06.627170. doi: 10.1101/2024.12.06.627170.
Natural antisense transcripts are expressed in eukaryotes, prokaryotes, and viruses and can possess regulatory functions at the transcriptional and/or post-transcriptional levels. studies have shown that HIV-1 antisense transcripts (AST) promote viral latency through epigenetic silencing of the proviral 5' long terminal repeat (LTR). However, expression of HIV-1 AST have not been convincingly demonstrated. Here, we used single RNA template amplification, detection, and sequencing to demonstrate expression of AST in unstimulated PBMC collected from people with HIV-1 (PWH). We found that AST had high genetic diversity that matched proviruses in cells from blood and lymph nodes. We measured a median of 26 copies of AST per 100 infected cells in PWH on ART and a median of 2 copies per 100 infected cells in PWH not on ART. The expression of HIV-1 AST is consistent with a potential regulatory role in regulation of HIV-1 expression.
天然反义转录本在真核生物、原核生物和病毒中均有表达，并可在转录和/或转录后水平发挥调控功能。研究表明，HIV-1反义转录本（AST）通过对前病毒5'长末端重复序列（LTR）的表观遗传沉默促进病毒潜伏。然而，HIV-1 AST的表达尚未得到令人信服的证实。在此，我们使用单RNA模板扩增、检测和测序来证明从HIV-1感染者（PWH）采集的未刺激外周血单核细胞（PBMC）中AST的表达。我们发现AST具有高度的遗传多样性，与来自血液和淋巴结细胞中的前病毒相匹配。我们测得接受抗逆转录病毒治疗（ART）的PWH每100个感染细胞中AST的中位数为26拷贝，未接受ART的PWH每100个感染细胞中AST的中位数为2拷贝。HIV-1 AST的表达与在HIV-1表达调控中的潜在调节作用一致。
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