转录活跃的缺陷型HIV-1前病毒及其与抗逆转录病毒治疗免疫无应答的关联

Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy.

作者信息

Scrimieri Francesca, Bastian Estella, Smith Mindy, Rehm Catherine A, Morse Caryn, Kuruppu Janaki, McLaughlin Mary, Chang Weizhong, Sereti Irini, Kovacs Joseph A, Lane H Clifford, Imamichi Hiromi

机构信息

Applied and Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

J Infect Dis. 2024 Jun 14;229(6):1786-1790. doi: 10.1093/infdis/jiae009.

DOI:10.1093/infdis/jiae009

PMID:38226493

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11175703/

Abstract

A subset of antiretroviral therapy-treated persons with human immunodeficiency virus (HIV), referred to as immunological nonresponders (INRs), fails to normalize CD4+ T-cell numbers. In a case-control study involving 26 INRs (CD4 < 250 cells/µL) and 25 immunological responders (IRs; CD4 ≥ 250 cells/µL), we evaluated the potential contribution of transcriptionally competent defective HIV-1 proviruses to poor CD4+ T-cell recovery. Compared to the responders, the INRs had higher levels of cell-associated HIV RNA (P = .034) and higher percentages of HLA-DR+ CD4+ T cells (P < .001). While not encoding replication-competent viruses, the RNA transcripts frequently encoded HIV-1 Gag-p17 and Nef proteins. These transcripts and/or resulting proteins may activate pathway(s) leading to the immunological nonresponse phenotype.

摘要

接受抗逆转录病毒治疗的一部分感染人类免疫缺陷病毒（HIV）的患者，被称为免疫无反应者（INR），其CD4 + T细胞数量未能恢复正常。在一项病例对照研究中，纳入了26名免疫无反应者（CD4＜250个细胞/µL）和25名免疫反应者（IR；CD4≥250个细胞/µL），我们评估了具有转录活性的缺陷型HIV-1前病毒对CD4 + T细胞恢复不佳的潜在影响。与反应者相比，免疫无反应者的细胞相关HIV RNA水平更高（P = 0.034），HLA-DR + CD4 + T细胞百分比更高（P＜0.001）。虽然这些RNA转录本不编码具有复制能力的病毒，但它们经常编码HIV-1 Gag-p17和Nef蛋白。这些转录本和/或产生的蛋白质可能激活导致免疫无反应表型的途径。