Neuropilin-1 is required for Lytic Replication in a Subset of Primary Effusion Lymphoma Cell Lines and for KSHV gene expression in Primary Endothelial Cells

ABSTRACT: Primary effusion lymphoma (PEL) is a B cell lymphoma that occur most often in people living with HIV/AIDS and caused by Kaposi sarcoma herpesvirus (KSHV). While newer regimens now exist, PEL still has poorer outcomes compared to other HIV-associated lymphomas. Since PEL B cells lack typical B cell markers, we aim to identify other surface proteins in disease cells that may act as possible diagnostic or prognostic markers. We performed single cell DNA-seq and antibody derived tag-seq on BCBL1 (KSHV+/EBV-) and LCL (KSHV-/EBV+ lymphoblastoid cell line) cells to determine which surface markers are specific for KSHV+ PEL. We identified Neuropilin-1 (NRP1) as a surface marker that is overexpressed in KSHV+ PEL cell lines (BCBL1, JSC1), but not in EBV+ LCL cells. NRP1 depletion during reactivation reduced lytic transcription, virion production and infectivity of NRP1+ PEL cell lines. Selected NRP1+ PEL cells also expressed higher levels of NANOG and OCT3/4 compared to controls. NRP1+ PEL cells had higher amounts of lytic transcripts. Overexpression of NRP1 resulted in higher lytic transcripts during lytic induction. Our findings suggest that NRP1 is a surface marker expressed for a subtype of PEL cells that is required for efficient lytic replication. It is also associated with increased expression of stemness markers, denoting poor prognosis in cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE327726 | GEO | 2026/09/08

REPOSITORIES: GEO