Kaposi's sarcoma-associated herpesvirus induces mitochondrial fission to evade host immune responses and promote viral production.

ABSTRACT: Mitochondrial dynamics are pivotal for host immune responses upon infection, yet how viruses manipulate these processes to impair host defence and enhance viral fitness remains unclear. Here we show that Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus also known as human herpesvirus 8, encodes Bcl-2 (vBcl-2), which reprogrammes mitochondrial architecture. It binds with NM23-H2, a host nucleoside diphosphate (NDP) kinase, to stimulate GTP loading of the dynamin-related protein (DRP1) GTPase, which triggers mitochondrial fission, inhibits mitochondrial antiviral signalling protein (MAVS) aggregation and impairs interferon responses in cell lines. An NM23-H2-binding-defective vBcl-2 mutant fails to evoke fission, leading to defective virion assembly due to activated MAVS-IF

SUBMITTER: Zhu Q 

PROVIDER: S-EPMC12337130 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature