Li Jian, Zhang Chuyu, Zou Zhenyi, Liang Yawen, Ma Peng, Lan Yun, Li Quanmin, Kong Qian, He Ruiying, Li Linghua, Chen Weilie
Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangzhou Key Laboratory of Clinical Pathogen Research for Infectious Diseases, Guangzhou, Guangdong, China.
Front Microbiol. 2025 Aug 21;16:1647986. doi: 10.3389/fmicb.2025.1647986. eCollection 2025.
Low-level viremia (LLV) in HIV infection, defined as detectable but low plasma viral load, is associated with an increased risk of virological failure (VF); however, the mechanisms underlying LLV remain unclear. Monocytes, as potential viral reservoirs, can migrate into tissues and differentiate into tissue-resident macrophage reservoirs, playing a critical role in viral dissemination and potentially driving persistent viremia.
This study aimed to analyze and compare the molecular characteristics of near-full-length HIV-1 proviral DNA quasispecies from monocytes in three distinct virological response groups: VF, LLV, and virological suppression (VS). Genetic diversity, drug resistance mutations (DRMs), and viral tropism were assessed.
Of the 198 single quasispecies sequences obtained from 54 patients, 177 were identified as near-full-length genomes (NFLGs; length >8.6 kb, without inversion). The VF group demonstrated a higher prevalence of intact proviruses (82.6%) compared to the LLV (50.0%) and VS groups (22.2%). Compared to the VF group, the LLV group exhibited significantly higher hypermutation rates (42.35% vs 8.78%, < 0.01) and greater median genetic distance (0.0446 vs 0.0186, < 0.01). Moreover, monocytes harbored proviral DNA with DRMs that were divergent from those detected in plasma RNA. No significant differences in viral tropism were observed across groups.
Near-full-length proviral quasispecies amplified from monocytes demonstrated distinct characteristics across virological response groups. Notably, proviral quasispecies in the LLV group exhibited higher genetic diversity, suggesting unique evolutionary dynamics under low-level viral replication. These findings underscore the importance of investigating proviral quasispecies within monocytes to better understand their role in persistent HIV viremia.
HIV感染中的低水平病毒血症（LLV），定义为可检测到但血浆病毒载量较低，与病毒学失败（VF）风险增加相关；然而，LLV背后的机制仍不清楚。单核细胞作为潜在的病毒储存库，可迁移到组织中并分化为组织驻留巨噬细胞储存库，在病毒传播中起关键作用，并可能导致持续性病毒血症。
本研究旨在分析和比较三个不同病毒学反应组（VF、LLV和病毒学抑制（VS））中单核细胞来源的近全长HIV-1前病毒DNA准种的分子特征。评估了遗传多样性、耐药突变（DRM）和病毒嗜性。
从54例患者中获得的198个单准种序列中，177个被鉴定为近全长基因组（NFLG；长度>8.6 kb，无倒置）。与LLV组（50.0%）和VS组（22.2%）相比，VF组完整前病毒的患病率更高（82.6%）。与VF组相比，LLV组表现出显著更高的超突变率（42.35%对8.78%，<0.01）和更大的中位遗传距离（0.0446对0.0186，<0.01）。此外，单核细胞携带的前病毒DNA中的DRM与血浆RNA中检测到的不同。各组之间在病毒嗜性方面未观察到显著差异。
从单核细胞中扩增的近全长前病毒准种在不同病毒学反应组中表现出不同特征。值得注意的是，LLV组中的前病毒准种表现出更高的遗传多样性，表明在低水平病毒复制下独特的进化动态。这些发现强调了研究单核细胞内前病毒准种以更好理解其在持续性HIV病毒血症中作用的重要性。
