Oncovirus-Driven Endothelial Plasticity: Endothelial-to-Mesenchymal Transition as a Hijacked Pathway in Oncoviral Cardiovascular Pathogenesis

Abstract

Oncoviruses utilise various molecular strategies to modulate host cells and induce microenvironments that favour viral persistence, immune evasion, and disease progression. Endothelial-to-mesenchymal transition (EndMT) has recently emerged as a critical, yet underrecognized, pathway hijacked by oncoviral pathogens to modulate endothelial plasticity within the cardiovascular system. Accumulating evidence indicates that Oncogenic and non-oncogenic viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV), and other endothelial-tropic viruses, directly manipulate host signalling networks, such as TGF-β, Wnt/β-catenin, Notch, and NF-κB, to induce partial or complete EndMT. This virus-driven EndMT contributes to vascular remodelling, chronic inflammation, aberrant angiogenesis, and the development of oncoviral-associated cardiovascular pathology and vascular tumours. The present review integrates current virological and mechanistic insights into EndMT as a hijacked host process, highlighting its role at the virus-host interface and discussing emerging antiviral and pathway-targeted strategies aimed at limiting oncovirus-mediated endothelial dysfunction.

Keywords: EndMT; HHV‐8; SARS‐CoV‐2; cardiovascular diseases; endothelial‐to‐mesenchymal transition.