Evidence for Multiple Subpopulations of Herpesvirus-Latently Infected Cells

Kaposi’s sarcoma-associated herpesvirus (KSHV)-associated primary effusion lymphomas (PEL) are traditionally viewed as homogenous regarding viral transcription and lineage of origin, but so far this contention has not been explored at the single-cell level. Single-cell RNA sequencing of latently infected PEL supports the existence of multiple subpopulations even within a single cell line. At most 1% of the cells showed evidence of near-complete lytic transcription. The majority of cells only expressed the canonical viral latent transcripts: those originating from the latency locus, the viral interferon regulatory factor locus, and the viral lncRNA nut-1/Pan/T1.1; however, a significant fraction of cells showed various degrees of more permissive transcription, and some showed no evidence of KSHV transcripts whatsoever. Levels of viral interleukin-6 (IL-6)/K2 mRNA emerged as the most distinguishing feature to subset KSHV-infected PEL. One newly uncovered phenotype is the existence of BCBL-1 cells that readily adhered to fibronectin and that displayed mesenchymal lineage-like characteristics.