Despite productive viral gene expression in the peripheral nervous system during acute
infection, the bovine herpesvirus 1 (BHV-1)
infection cycle is blocked in sensory ganglionic neurons and consequently latency is established. The only abundant viral transcript expressed during latency is the latency-related (LR)
RNA. LR gene products inhibit S-phase entry, and binding of the LR
protein (LRP) to
cyclin A was hypothesized to block cell cycle progression. This study demonstrates LRP is a
nuclear protein which is expressed in neurons of latently infected cattle. Affinity chromatography indicated that LRP interacts with
cyclin-dependent kinase 2 (cdk2)-cyclin complexes or cdc2-cyclin complexes in transfected human cells or infected bovine cells. After partial purification using three different columns (
DEAE-
Sepharose, Econo S, and
heparin-agarose), LRP was primarily associated with cdk2-cyclin E complexes, an
enzyme which is necessary for G1-to-S-phase cell cycle progression. During acute
infection of trigeminal ganglia or following
dexamethasone-induced reactivation, BHV-1 induces expression of
cyclin A in neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807-3814, 1996). Expression of S-phase regulatory
proteins (
cyclin A, for example) leads to neuronal apoptosis. Consequently, we hypothesize that interactions between LRP and
cell cycle regulatory proteins promote survival of postmitotic neurons during acute
infection and/or reactivation.