Cross-omics mapping of the human HIV restrictome across clinical states, immune-cell compartments, and protein responses
- 1Department of Microbiology and Parasitology, Faculty of Medicine, St. Francis University College of Health and Allied Sciences, Ifakara, Tanzania
Abstract
Host restriction factors can block HIV at multiple stages, but they are often studied as individual genes or within a single molecular layer. I performed an evidence-structured computational reanalysis of three independent public datasets to determine how the human HIV restrictome varies across clinical states, immune-cell compartments, and protein responses. The analysis used bulk monocyte RNA sequencing (GSE157198), PBMC single-cell/CITE-seq data (GSE256089), and primary CD4 T-cell proteomics (PXD012263) within a prespecified restrictome-immunometabolism framework. In GSE157198, ART-naive monocytes had higher core-restrictome activity than healthy controls (difference = 1.154, p = 0.000746), and core scores were strongly correlated with interferon/innate-sensing scores (Spearman r = 0.800, p = 7.47 × 10^-11). Core-lipid/cholesterol correlation was weaker and was not independent of interferon after conditional analysis. In GSE256089, participant-paired core-restrictome scores were enriched in NK cells relative to B cells, monocytes, and T cells, and matched random-gene-set analyses supported enrichment beyond background expression structure. FCGR3A monocytes also had higher participant-paired core scores than CD14 monocytes. Exploratory sensing/death-gene analysis identified cell-type-specific expression patterns but did not establish pathway activation, pyroptosis, or apoptosis. In PXD012263, the historical q < 0.05 proteomic selection contained 19 curated genes and retained mixed response polarity; sensitivity thresholds q < 0.01 and q < 0.10 selected 10 and 25 genes, respectively. Together, the results show that HIV restrictome activity varies across clinical and immune-cell contexts and is embedded within broader interferon-linked and immunometabolic states. Because the datasets are independent and not subject matched, the findings are observational and hypothesis-generating rather than causal.
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BibTeX
@article{maghembe2026crossomics,
title = {{Cross-omics mapping of the human HIV restrictome across clinical states, immune-cell compartments, and protein responses}},
author = {Reuben S. Maghembe},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0356591},
url = {https://doi.org/10.1371/journal.pone.0356591},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cross-omics mapping of the human HIV restrictome across clinical states, immune-cell compartments, and protein responses
AU - Reuben S. Maghembe
PY - 2026
DA - 2026/10/13
JO - PLOS One
DO - 10.1371/journal.pone.0356591
UR - https://doi.org/10.1371/journal.pone.0356591
AB - Host restriction factors can block HIV at multiple stages, but they are often studied as individual genes or within a single molecular layer. I performed an evidence-structured computational reanalysis of three independent public datasets to determine how the human HIV restrictome varies across clinical states, immune-cell compartments, and protein responses. The analysis used bulk monocyte RNA sequencing (GSE157198), PBMC single-cell/CITE-seq data (GSE256089), and primary CD4 T-cell proteomics (PXD012263) within a prespecified restrictome-immunometabolism framework. In GSE157198, ART-naive monocytes had higher core-restrictome activity than healthy controls (difference = 1.154, p = 0.000746), and core scores were strongly correlated with interferon/innate-sensing scores (Spearman r = 0.800, p = 7.47 × 10^-11). Core-lipid/cholesterol correlation was weaker and was not independent of interferon after conditional analysis. In GSE256089, participant-paired core-restrictome scores were enriched in NK cells relative to B cells, monocytes, and T cells, and matched random-gene-set analyses supported enrichment beyond background expression structure. FCGR3A monocytes also had higher participant-paired core scores than CD14 monocytes. Exploratory sensing/death-gene analysis identified cell-type-specific expression patterns but did not establish pathway activation, pyroptosis, or apoptosis. In PXD012263, the historical q < 0.05 proteomic selection contained 19 curated genes and retained mixed response polarity; sensitivity thresholds q < 0.01 and q < 0.10 selected 10 and 25 genes, respectively. Together, the results show that HIV restrictome activity varies across clinical and immune-cell contexts and is embedded within broader interferon-linked and immunometabolic states. Because the datasets are independent and not subject matched, the findings are observational and hypothesis-generating rather than causal.
SN - 1932-6203
ER -