Single-Cell Sequencing of Peripheral Blood Mononuclear Cells Reveals Immune Landscape of Monkeypox Patients with HIV

The monkeypox (MPXV) outbreak in 2022 is more prevalent among individuals with human immunodeficiency virus (HIV). While it is plausible that HIV-induced immunosuppression could result in a more severe progression, the exact mechanisms remain undetermined. To better understand the immunopathology of MPXV in patients with and without HIV infection, we employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from 6 patients hospitalized for MPXV, 3 of whom had HIV infection (HIV antibody positive & HIV RNA level below the detection limit), and 3 patients only infected with MPXV (HIV-). We map the peripheral immune response in both the acute phase and the recovery period, showing the reconfiguration of peripheral immune cell phenotypes in acute stage compared with recovery stage of 6 patients, characterized by disturbed cell subsets and intense cell interactions mediated by monocytes and neutrophils. Importantly, besides different Mono/DC dynamic between HIV + and HIV- patients, HIV + patients showed decreased NK cells subsets and expansion of some CD8 T cell subsets, we also found obviously dysregulated gene expression in B cells, thus proposing mechanism underlying serious condition underlying HIV + patients. In conclusion, our findings provide a comprehensive cell atlas of MPXV patients, shed light on the mechanisms underlying the severe disease progression and longer recovery time in HIV + individuals.