Single-cell transcriptomic profiling reveals unique monocyte responsiveness to HIV-2 viremia

ABSTRACT: Both HIV-1 and HIV-2 cause AIDS, but disease progression is slower in HIV-2 infection, and in contrast to HIV-1, many HIV-2 infected individuals present with undetectable plasma viral load (pVL). The underlying mechanisms behind these differences are not elucidated. To disentangle the transcriptomic landscape in HIV-2 infection in relation to viremia, and compared to HIV-1 infection, we performed single-cell RNA-sequencing analysis on PBMCs from HIV-1 viremic, HIV-2 viremic, HIV-2 aviremic and HIV-negative individuals. Most notably, a strong monocyte responsiveness to HIV-2 viremia was observed, even though pVL was 10-fold lower than in HIV-1 viremic individuals. Additionally, HIV-2 viremic infection was distinguished from HIV-1 viremic infection by monocytic expression of genes encoding antiviral proteins, including entry inhibiting CCR5 ligands CCL3L1, CCL4 and CCL4L2 and interferon-stimulated genes IFI6 and IFI27. Gene-set enrichment analysis also suggested enrichment of the process “Antigen processing and presentation” in HIV-2 viremic individuals. Collectively, our results contribute to the understanding of HIV-2 pathogenesis, and suggest that monocytes in chronic HIV-2, in contrast to HIV-1, infection maintain the capacity to respond to viremia. Furthermore, HIV-2 induced upregulation of genes with antiviral and antigen presentation functions in monocytes, highlighting a currently unrecognized role that monocytes may play in HIV-2 infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242699 | GEO | 2025/05/30

REPOSITORIES: GEO