Human herpesvirus 8 viral cyclin protein (v-cyclin)

The Human herpesvirus 8 (HHV-8) viral cyclin protein, also known as v-cyclin or K-cyclin, is a viral homolog of cellular D-type cyclins encoded by the ORF72 gene [1, 4]. It is a key oncoprotein involved in the development of HHV-8-associated malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD) [2, 7]. v-cyclin functions by constitutively activating host cyclin-dependent kinase 6 (CDK6), and to a lesser extent CDK2, CDK4, and CDK9, which leads to the phosphorylation of the retinoblastoma (Rb) protein and the bypass of G1/S cell cycle checkpoints [4, 11, 14]. A defining characteristic of the v-cyclin/CDK6 complex is its resistance to endogenous CDK inhibitors such as p16INK4a, p21Cip1, and p27Kip1, which normally regulate the cell cycle [4, 14]. This persistent activation promotes uncontrolled cell proliferation, inhibits apoptosis, and induces DNA damage, contributing to viral oncogenesis [4, 18]. Recent studies have highlighted the v-cyclin/CDK6 axis as a therapeutic vulnerability, demonstrating that CDK4/6 inhibitors like palbociclib can effectively reduce viral replication and tumor growth in preclinical models [8].

Other names

ORF72KSHV cyclinK-cyclinKaposi's sarcoma-associated herpesvirus cyclin

Inhibition of the cyclin-dependent kinase 6 (CDK6) activity induced by v-cyclin to block cell cycle progression and viral oncogenesis.