# Single-Cell Transcriptomic Profile Associated with Sub-Subtype A6 and CRF63-02A6 HIV-1 Strain Infection

## TL;DR

This study uses single-cell RNA sequencing to analyze immune responses in early HIV-1 infection caused by sub-subtypes A6 and CRF63-02A6, which are common in Russia and the FSU.

## Contribution

The paper provides the first single-cell transcriptional atlas of immune responses to HIV-1 sub-subtypes A6 and CRF63-02A6 during acute infection.

## Key findings

- Early HIV-1 infection causes significant reorganization of immune cell transcriptional programs.
- Pro-inflammatory pathways and metabolic adaptations are activated in key immune cells.
- Dysregulation of TGF-β and mTOR signaling is observed, along with altered intercellular communication.

## Abstract

We present the single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMC) from individuals during acute HIV-1 infection caused by viral strains circulating in Russia and the Former Soviet Union (FSU) countries. Using 10x Genomics single-cell RNA sequencing (scRNA-seq) on the Illumina NextSeq 550 platform, we have analyzed scRNA-seq data from three treatment-naive patients (viral load > 1 × 106 copies/mL, estimated infection duration ≤ 4 weeks) and three healthy donors. Data integration (Seurat, Harmony), automated cell-type annotation (CellTypist), and GeneOntology (GO) enrichment analysis for highly expressed and low-expressed genes revealed a profound reorganization of transcriptional programs across key immune populations, including memory CD4+ and CD8+ T cells, non-classical monocytes and natural killer cells (NK-cells). We observed signatures of hyperactivation of pro-inflammatory pathways (NF-kB, TNF, and type I/II interferon signaling), upregulation of genes associated with cellular migration (CXCR4, CCR7) and metabolic adaptation (oxidative phosphorylation components), alongside a mixed pro- and anti-apoptotic expression profile. Notably, our data pointed to a pronounced dysregulation of the TGF-β and mTOR signaling cascades, disrupted intercellular communication networks—particularly between cytotoxic cells and their regulators—altered expression of genes implicated in disease progression (OLR1, SERPINB2, COPS9) and viral persistence control (NEAT1, NAF1). This work provides an initial single-cell transcriptional atlas characterizing early immune responses to HIV-1 sub-subtypes A6 and CRF63_02A6, the predominant drivers of the HIV epidemic across the FSU region.