Hematopoietic Stem and Progenitor Cells Are a Distinct HIV Reservoir that Contributes to Persistent Viremia in Suppressed Patients

Abstract

Highlights d Hematopoietic stem and progenitor cells can serve as longterm reservoirs of HIV d HSPCs harbor both infectious and defective proviral genomes d HSPCs are an important source of residual plasma virus in treated people d Clonally amplified HIV proviruses contribute to residual plasma virus

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

“…Viral DNA has also been detected in hematopoietic stem cells (HSCs) from ART-treated patients, which could demonstrate their involvement in HIV-1 persistence (Sebastian et al, 2017;Zaikos et al, 2018). Despite the limited infection and detection of HSCs in a subset of patients (McNamara et al, 2013), their role as a viral reservoir may be crucial.…”

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

“…While it remains unclear whether infected HSPCs contribute to residual viremia after ART Mcnamara and Collins, 2011), a recent article reported that HSPCs in suppressed patients harbor functional HIV proviral genomes that often match residual peripheral viral RNA (Zaikos et al, 2018). If these findings are confirmed, HSPCs might be finally regarded as long-term viral reservoirs, because they are long-lived cells with regulated susceptibility to apoptosis (Durdik et al, 2017).…”

The Impact of Cellular Proliferation on the HIV-1 Reservoir

“…HSPCs express CD4 at low levels, are capable of being infected with both X4 and R5-tropic HIV in vitro, and proviral sequences have been identified in HSPCs from patients [11,12,16,22]. Identical proviral sequences, including the same insertion site in the patient genome, were found in multiple compartments of the hematopoietic lineage including HSPCs, PBMCs (peripheral blood mononuclear cells), and BMMCs (bone marrow mononuclear cells).…”

“…Identical proviral sequences, including the same insertion site in the patient genome, were found in multiple compartments of the hematopoietic lineage including HSPCs, PBMCs (peripheral blood mononuclear cells), and BMMCs (bone marrow mononuclear cells). A subset of these clonal sequences was matched to expressed cell-free virus [11]. Some cells with clonal proviral sequences matching provirus from HSPCs were not CD4+.…”

“…The large majority of proviral sequences in an individual are defective [6], meaning they are incapable of producing virus that can infect new cells. Both defective and replication-competent HIV sequences have been found in clonally expanded cells [7][8][9][10][11][12]. In addition to CD4+ T cells, HIV targets multiple CD4+ cell types in the hematopoietic compartment including macrophages and hematopoietic stem cells, each with a different proliferative potential and ability to contribute to maintenance of the latent reservoir [11][12][13][14][15][16].…”