The latency-related (LR) RNA encoded by bovine herpesvirus 1 is abundantly expressed in the trigeminal ganglia of latently infected calves. Expression of LR proteins is necessary for reactivation from latency and the protection of infected neurons from apoptosis. In this study, we demonstrated that an LR-encoded protein, open reading frame 2 (ORF-2), or ORF-2 fusion proteins encoded by alternatively spliced LR transcripts inhibit cold shock or Fas ligand-induced apoptosis in mouse neuroblastoma (neuro-2A) cells. Frameshift mutants of ORF-2 do not inhibit apoptosis, which suggests that protein expression, not LR RNA expression, mediates the antiapoptotic activity of the LR gene in transfected neuro-2A cells.