Oncolytic HSV1716 Attenuates Tumor‑Killing Activity of Infected NK Cells

In this study, we examined interactions between the HSV‑1–derived oncolytic virus HSV1716 and primary human NK cells. Co‑culture experiments revealed increased activation and degranulation of NK cells in response to HSV1716‑infected tumor cells, despite the downregulation of ligands for NK‑cell activating receptors on infected targets.

Following co-culture with infected tumor cells, but not after incubation with viral inoculum alone, viral gene expression and increased viral copy numbers were detected in NK cells, indicating enhanced viral acquisition and persistence associated with target-cell contact. HSV1716-infected NK cells displayed impaired tumor cell killing ability. Single-cell sequencing analysis revealed downregulation of key NK effector genes alongside alterations in stress-response pathways in HSV1716 infected NK cells.