PNMA2 forms non-enveloped virus-like capsids that trigger paraneoplastic neurological syndrome.

ABSTRACT: The paraneoplastic Ma antigen (PNMA) genes are associated with cancer-induced paraneoplastic syndromes that present with neurological symptoms and autoantibody production. How PNMA proteins trigger a severe autoimmune disease is unclear. PNMA genes are predominately expressed in the central nervous system with little known functions but are ectopically expressed in some tumors. Here, we show that PNMA2 is derived from a Ty3 retrotransposon that encodes a protein which forms virus-like capsids released from cells as non-enveloped particles. Recombinant PNMA2 capsids injected into mice induce a robust autoimmune reaction with significant generation of autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, while capsid-assembly-defective PN

SUBMITTER: Xu J 

PROVIDER: S-EPMC9934673 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature