Analysis of a bovine herpesvirus 1 protein encoded by an alternatively spliced latency related (LR) RNA that is abundantly expressed in latently infected neurons

- BHV-1 proteins, ORF2 and a similar protein (15d ORF) are detected in latently infected neurons.
- Relative to ORF2, the 15d ORF is more stable in transfected cells.
- The 15d ORF and ORF2 inhibit Notch-dependent signaling.
- ORF2 and the 15d ORF bind DNA.

The bovine herpes virus 1 (BoHV-1) encoded latency-related RNA (LR-RNA) is abundantly expressed in latently infected sensory neurons. A LR mutant virus with three stop codons at the amino-terminus of ORF2 does not reactivate from latency or replicate efficiently in certain tissues. ORF2 inhibits apoptosis, interacts with Notch1 or Notch3, and interferes with Notch mediated signaling. Alternative splicing of LR-RNA in trigeminal ganglia yields transcripts that have the potential to encode a protein containing most of ORF2 sequences and parts of other coding sequences located within the LR gene. In this study, we determined that an ORF2 protein fused with reading frame B (15d ORF) was more stable in transfected cells. ORF2 and the 15d ORF stimulated neurite formation in mouse neuroblastoma cells, interfered with Notch3 mediated trans-activation, and had similar DNA binding properties. Increased stability of the 15d ORF is predicted to enhance the establishment of latency.