Plasma proteomics analysis of Chinese HIV-1 infected individuals focusing on the immune and inflammatory factors afford insight into the viral control mechanism

Front Immunol. 2024 May 10:15:1378048. doi: 10.3389/fimmu.2024.1378048. eCollection 2024.

Abstract

Background: Long-term non-progressors (LTNPs) with HIV infection can naturally control viral replication for up to a decade without antiretroviral therapy (ART), but the underlying mechanisms of this phenomenon remain elusive.

Methods: To investigate the relevant immune and inflammatory factors associated with this natural control mechanism, we collected plasma samples from 16 LTNPs, 14 untreated viral progressors (VPs), 17 successfully ART-treated patients (TPs), and 16 healthy controls (HCs). The OLINK immune response panel and inflammation panel were employed to detect critical proteins, and the plasma neutralizing activity against a global panel of pseudoviruses was assessed using TZM-bl cells.

Results: The combination of IL17C, IL18, DDX58, and NF2 contributed to discriminating LTNPs and VPs. IL18 and CCL25 were positively associated with CD4+ T cell counts but negatively correlated with viral load. Furthermore, CXCL9 and CXCL10 emerged as potential supplementary diagnostic markers for assessing the efficacy of antiretroviral therapy (ART). Finally, TNFRSF9 displayed positive correlations with neutralization breadth and Geometry Median Titer (GMT) despite the lack of significant differences between LTNPs and VPs.

Conclusion: In summary, this study identified a set of biomarkers in HIV-infected individuals at different disease stages. These markers constitute a potential network for immune balance regulation in HIV infection, which is related to the long-term control of HIV by LTNPs. It provides important clues for further exploring the immune regulatory mechanism of HIV.

Keywords: HIV; cytokine; immune balance regulation; long-term non-progressor (LTNP); neutralizing activity; plasma; proteomics.

MeSH terms

  • Adult
  • Biomarkers* / blood
  • CD4 Lymphocyte Count
  • China
  • East Asian People
  • Female
  • HIV Infections* / blood
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • HIV Infections* / virology
  • HIV Long-Term Survivors
  • HIV-1* / immunology
  • Humans
  • Male
  • Middle Aged
  • Proteomics* / methods
  • Viral Load*
  • Virus Replication / drug effects

Substances

  • Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (NO. 81872680, 32371002 and 81861138011), National Key Research and Development Program of China (NO. 2022YFC2305201), and Beijing Natural Science Foundation(M21015).