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Three immunoregulatory signatures define non-productive HIV infection in CD4+ T memory stem cells

ABSTRACT: The persistent HIV reservoir constitutes the main obstacle to curing HIV/AIDS disease. Our understanding of how non-productive HIV infections are established in primary human CD4+ T cells during the first round of infection remains, however, incomplete. In this study, we leveraged the HIV reporter virus pMorpheus-V5 to delineate cellular expression patterns that are upregulated in non-productively infected primary CD4+ T memory stem cells (TSCM). We found that CD4+ TSCM harboring non-productive proviruses displayed a distinct transcriptomic signature comprising 118 upregulated genes. This non-productive expression profile was distinct from that of productively infected cells as well as from negative-exposed and mock-infected cells. Among the cellular genes most upregulated in CD4+ T cells harboring non-productive proviruses were CCR4-binding migratory chemokines (CCL22 and CCL17), tryptophan catabolic enzymes (IDO1 and KYNU), and genes encoding cytoskeletal rearrangement proteins (BASP1 and TNFAIP2). Intra-cellular FACS-based analyses revealed that non-productively infected CD4+ TSCM cells were enriched (i.e., 8.3%) for CCL22 and IDO1 co-expression compared to the other CD4+ memory subsets, underscoring a clear CD4+ T cell subset specificity for the upregulation of these two immune gene sets associated with non-productive infections. These findings suggest that primary human CD4+ TSCMharboring non-productive proviruses display a distinct immunoregulatory phenotype.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309709 | GEO | 2026/05/15

REPOSITORIES: GEO

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Three immunoregulatory signatures define non-productive HIV infection in CD4+ T memory stem cells

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