Department of Laboratory Medicine, Lund University, Lund, Sweden.
Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Leuven, Belgium.
mBio. 2019 Jan 8;10(1):e01245-18. doi: 10.1128/mBio.01245-18.
A positive correlation between virus evolutionary rate and disease progression has been shown for human immunodeficiency virus type 1 (HIV-1) infection. Much less is known about HIV-2, the second causative agent of AIDS. We analyzed 528 HIV-2 V1-C3 sequences generated from longitudinal plasma samples that were collected from 16 study participants during a median observation time of 7.9 years (interquartile range [IQR], 5.2 to 14.0 years). Study participants were classified as faster or slower disease progressors based on longitudinal CD4 T-cell data. The HIV-2 evolutionary rate was significantly associated with CD4 T-cell levels and was almost twice as high among the faster progressors as among the slower progressors. Higher evolutionary rates were accounted for by both synonymous and nonsynonymous nucleotide substitutions. Moreover, slow disease progression was associated with stronger positive selection on HIV-2/SIVsm (simian immunodeficiency virus infecting sooty mangabey) surface-exposed conserved residues. This study demonstrated a number of previously unknown characteristics linking HIV-2 disease progression with virus evolution. Some of these findings distinguish HIV-2 from HIV-1 and may contribute to the understanding of differences in pathogenesis. The relationship between HIV evolution and disease progression is fundamental to our understanding of HIV immune control and vaccine design. There are no clear definitions for faster and slower HIV-2 disease progression and for the relationship of the rate of progression with HIV-2 evolution. To address the hypothesis that viral evolution is correlated with disease progression in HIV-2 infection, we determined faster and slower disease progression based on follow-up data from a prospective cohort of police officers in Guinea-Bissau. The analysis showed that although the CD4 T-cell level and the decline in the level were independently associated with progression to AIDS, only the CD4 T-cell level or a combined CD4 T-cell level/decline stratification was associated with the rate of HIV-2 evolution. The HIV-2 evolutionary rate was almost twice as high among the faster progressors as among the slower progressors. Importantly, this report defines previously unknown characteristics linking HIV-2 disease progression with virus evolution.
已证实人类免疫缺陷病毒 1 型（HIV-1）感染的病毒进化率与疾病进展呈正相关。对于 HIV-2，即艾滋病的第二种致病因子，人们了解得要少得多。我们分析了从 16 名研究参与者的纵向血浆样本中生成的 528 个 HIV-2 V1-C3 序列，这些样本是在中位观察时间为 7.9 年（四分位间距[IQR]，5.2 至 14.0 年）期间收集的。根据纵向 CD4 T 细胞数据，将研究参与者分为疾病进展较快者和较慢者。HIV-2 的进化率与 CD4 T 细胞水平显著相关，在进展较快者中的 HIV-2 进化率几乎是进展较慢者的两倍。较高的进化率归因于同义核苷酸取代和非同义核苷酸取代。此外，较慢的疾病进展与 HIV-2/SIVsm（感染黑长尾猴的猴免疫缺陷病毒）表面暴露保守残基的正选择更强相关。本研究证明了一些以前未知的特征，将 HIV-2 疾病进展与病毒进化联系起来。其中一些发现将 HIV-2 与 HIV-1 区分开来，并可能有助于了解发病机制的差异。病毒进化与疾病进展之间的关系是我们理解 HIV 免疫控制和疫苗设计的基础。目前尚无关于 HIV-2 疾病进展较快和较慢的明确定义，也没有关于进展速度与 HIV-2 进化关系的明确定义。为了验证病毒进化与 HIV-2 感染中的疾病进展相关的假设，我们根据来自几内亚比绍的警察前瞻性队列的随访数据确定了疾病进展较快和较慢的情况。分析表明，尽管 CD4 T 细胞水平和水平下降与艾滋病进展独立相关，但只有 CD4 T 细胞水平或 CD4 T 细胞水平/下降的联合分层与 HIV-2 进化的速度相关。在进展较快者中的 HIV-2 进化率几乎是进展较慢者的两倍。重要的是，本报告定义了以前未知的特征，将 HIV-2 疾病进展与病毒进化联系起来。
