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<p>CMV seropositivity contributes to medical complications in people living with HIV (PLHIV). This study provides a comprehensive evaluation of how CMV seropositivity shapes the immune system of 1,887 PLHIV, by utilizing multi-omics and deep immune phenotyping datasets. The study measured the immune cell profiles from whole blood, and the cytokine production of PBMCs exposed to various ex-vivo stimuli. We observed an increase in pro-inflammatory cytokine production of circulating immune cells and differences in phenotype of innate-like lymphocyte populations associated with CMV seropositivity. This study also measured 5-omics layers, including genomics, DNA methylation, transcriptomics, and plasma protein and metabolites. The DNA methylome and transcriptome demonstrated prominent CMV-induced signatures related to immune functions in PLHIV. Particularly, high <i>FCRL6</i> expression is a promising biomarker for immune activation, underlined by the demethylation of <i>FCRL6</i> and up-regulation of gene expression and plasma protein concentrations in CMV-seropositive PLHIV. Host genetics-driven elevation in both gene and protein expression of FCRL6 was also associated with latent CMV infection. A significant CMV-seroprevalence locus was associated with cytokine production capacity and protein abundance. Mendelian randomization analyses demonstrated a causal relationship between elevated <i>FCRL6</i> expression and CMV seropositivity.</p>

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Molecular signatures and causal factors underlying latent cytomegalovirus infection among people living with HIV (PLHIV)

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月25日

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  • Nhan Nguyen,
  • Zhenhua Zhang,
  • Xun Jiang,
  • Nienke van Unen,
  • Jéssica C. dos Santos,
  • Liang Zhou,
  • Vasiliki Matzaraki,
  • Javier Botey-Bataller,
  • Marc Blaauw,
  • Wilhelm A. J. W. Vos,
  • Louise van Eekeren,
  • Annelies Verbon,
  • Albert L. Groenendijk,
  • Janneke E. Stalenhoef,
  • Marvin A. H. Berrevoets,
  • Leo A. B. Joosten,
  • Mihai G. Netea,
  • Cheng-Jian Xu,
  • André J. A. M. van der Ven,
  • Yang Li

摘要

CMV seropositivity contributes to medical complications in people living with HIV (PLHIV). This study provides a comprehensive evaluation of how CMV seropositivity shapes the immune system of 1,887 PLHIV, by utilizing multi-omics and deep immune phenotyping datasets. The study measured the immune cell profiles from whole blood, and the cytokine production of PBMCs exposed to various ex-vivo stimuli. We observed an increase in pro-inflammatory cytokine production of circulating immune cells and differences in phenotype of innate-like lymphocyte populations associated with CMV seropositivity. This study also measured 5-omics layers, including genomics, DNA methylation, transcriptomics, and plasma protein and metabolites. The DNA methylome and transcriptome demonstrated prominent CMV-induced signatures related to immune functions in PLHIV. Particularly, high FCRL6 expression is a promising biomarker for immune activation, underlined by the demethylation of FCRL6 and up-regulation of gene expression and plasma protein concentrations in CMV-seropositive PLHIV. Host genetics-driven elevation in both gene and protein expression of FCRL6 was also associated with latent CMV infection. A significant CMV-seroprevalence locus was associated with cytokine production capacity and protein abundance. Mendelian randomization analyses demonstrated a causal relationship between elevated FCRL6 expression and CMV seropositivity.