Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China.
Viruses. 2022 Mar 30;14(4):719. doi: 10.3390/v14040719.
Pulmonary microbial invasion frequently occurs during AIDS progression in HIV patients. Inflammatory cytokines and other immunoregulatory factors play important roles in this process. We previously established an AIDS model of SIVmac239 infection in northern pig-tailed macaques (NPMs), which were divided into rapid progressor (RP) and slow progressor (SP) groups according to their AIDS progression rates. In this study, we performed 16S rDNA and transcriptome sequencing of the lungs to reveal the molecular mechanism underlying the difference in progression rate between the RPs and SPs. We found that microbial invasion in the RP group was distinct from that in the SP group, showing marker flora of the , and , and more . Through pulmonary transcriptome analysis, we found that the transcription factor ZNF683 had higher expression in the SP group than in the RP group. In subsequent functional experiments, we found that ZNF683 increased the proliferation and IFNγ secretion ability of CD8+ T cells, thus decreasing SIV or HIV replication, which may be related to AIDS progression in SIVmac239-infected NPMs. This study helps elucidate the various complexities of disease progression in HIV-1-infected individuals.
肺部微生物入侵在 HIV 患者的艾滋病进展中经常发生。炎症细胞因子和其他免疫调节因子在这个过程中起着重要作用。我们之前在北方长尾猕猴（NPM）中建立了 SIVmac239 感染的艾滋病模型，根据其艾滋病进展速度将其分为快速进展者（RP）和缓慢进展者（SP）组。在这项研究中，我们对肺部进行了 16S rDNA 和转录组测序，以揭示 RP 和 SP 组之间进展速度差异的分子机制。我们发现 RP 组中的微生物入侵与 SP 组不同，表现出 、 和 的标志菌群，并且更多。通过肺部转录组分析，我们发现转录因子 ZNF683 在 SP 组中的表达高于 RP 组。在随后的功能实验中，我们发现 ZNF683 增加了 CD8+T 细胞的增殖和 IFNγ 分泌能力，从而降低了 SIV 或 HIV 的复制，这可能与 SIVmac239 感染的 NPM 中的艾滋病进展有关。这项研究有助于阐明 HIV-1 感染者疾病进展的各种复杂性。
