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Omics · study · 2026

The HIV-1 Vpr R77Q mutant alters host apoptotic gene regulation in CD4+ T cells

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HIV-1 viral protein R (Vpr) is a multifunctional protein central to HIV-1 pathogenesis and progression to AIDS.

Description

Polymorphisms in vpr have been linked to varying rates of HIV-1 progression. Of note is the HIV-1 Vpr R77Q mutant, associated with delayed progression to AIDS.

We previously demonstrated that the R77Q mutant promotes a non-inflammatory, apoptotic phenotype in CD4+ T cells. To investigate the mechanism underlying the R77Q-induced apoptotic phenotype, we performed RNA sequencing on a CD4+ T cell line, HUT78, infected with either a replication-competent wild-type strain (NL4-3) or the R77Q mutant. Our results show that at 72 hours post-infection, transcriptomes were heterogeneous, and differential expression analysis identified 289 differentially expressed genes (DEGs) in the R77Q vs. WT comparison.

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Functional enrichment analysis revealed enriched pathways associated with apoptosis. Gene ontology (GO) terms and GO connections also revealed an apoptotic signature. Although both viral strains upregulated pro-apoptotic genes, the R77Q mutant failed to upregulate some key anti-apoptotic genes such as bcl-2, while WT-infected cells displayed upregulation of those anti-apoptotic genes.

Predicted protein-protein interaction within the Bcl-2 family local network also suggests that interactions within this network were significantly different. Taken together, these findings provide a transcriptomic basis for our previous observations of enhanced apoptosis in R77Q-infected cells and highlight distinct host cell responses that may underlie delayed HIV-1 progression. These results may be useful in identifying new targets to delay AIDS progression.

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Life Sciences
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RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE31913915 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title