Although viral gene expression occurs in the peripheral nervous system during acute
infection, bovine herpesvirus 1 (BHV-1) gene expression is extinguished, many neurons survive, and latency ensues. The only abundant viral transcript expressed during latency is the latency-related (LR)
RNA, which is alternatively spliced in trigeminal ganglia during acute
infection (L. Devireddy and C. Jones, J. Virol. 72:7294-7301, 1998). A subset of neurons express a
protein encoded by the LR gene and the LR
protein (LRP) is associated with
cyclin-dependent kinase 2 (Cdk2)/
cyclin complexes during productive
infection (Y. Jiang, A. Hossain, M. T. Winkler, T. Holt, A. Doster, and C. Jones, J. Virol. 72:8133-8142, 1998). LR gene products inhibit cell cycle progression, perhaps as a result of LRP interacting with Cdk2/
cyclin complexes. During acute
infection, expression of
cyclin A occurs in trigeminal ganglionic neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807-3814, 1996). Inappropriate expression of G(1)- and S-phase
cyclins can initiate programmed cell death (PCD), apoptosis, in neurons, suggesting that LR gene products inhibit PCD. To test this hypothesis, we modified an assay to measure PCD frequency in transiently transfected cells.
C(6)-ceramide,
fumonisin B(1) (FB(1)), or
etoposide was used to initiate PCD following transfection of cells with plasmids expressing LR gene products and the
beta-galactosidase gene. Transfected cells that survived were quantified by counting
beta-galactosidase-positive cells. Plasmids that expressed LR gene products promoted survival of monkey kidney (CV-1), human lung (IMR-90), or mouse
neuroblastoma (neuro-2A) cells after induction of PCD. Plasmids with
termination codons at the beginning of LR open reading frames or deletion of sequences that mediate splicing of LR
RNA did not promote cell survival following PCD induction. We hypothesize that LR gene products play a role in promoting survival of postmitotic neurons during acute
infection or reactivation.