PMID- 22139602 OWN - NLM STAT- MEDLINE DCOM- 20130213 LR - 20211021 IS - 1538-2443 (Electronic) IS - 1355-0284 (Linking) VI - 17 IP - 6 DP - 2011 Dec TI - Regulation of the latency-reactivation cycle by products encoded by the bovine herpesvirus 1 (BHV-1) latency-related gene. PG - 535-45 LID - 10.1007/s13365-011-0060-3 [doi] AB - Like other alpha-herpesvirinae subfamily members, the primary site for bovine herpesvirus 1 (BHV-1) latency is ganglionic sensory neurons. Periodically BHV-1 reactivates from latency, virus is shed, and consequently virus transmission occurs. Transcription from the latency-related (LR) gene is readily detected in neurons of trigeminal ganglia (TG) of calves or rabbits latently infected with BHV-1. Two micro-RNAs and a transcript encompassing a small open reading frame (ORF-E) located within the LR promoter can also be detected in TG of latently infected calves. A BHV-1 mutant that contains stop codons near the beginning of the first open reading frame (ORF2) within the major LR transcript (LR mutant virus) has been characterized. The LR mutant virus does not express ORF2, a reading frame that lacks an initiating ATG (reading frame B), and has reduced expression of ORF1 during productive infection. The LR mutant virus does not reactivate from latency following dexamethasone treatment suggesting that LR protein expression regulates the latency-reactivation cycle. Higher levels of apoptosis occur in TG neurons of calves infected with the LR mutant viruses when compared to wild-type BHV-1 indicating that the anti-apoptotic properties of the LR gene is necessary for the latency-reactivation cycle. ORF2 inhibits apoptosis and regulates certain viral promoters, in part, because it interacts with three cellular transcription factors (C/EBP-alpha, Notch1, and Notch3). Although ORF2 is important for the latency-reactivation cycle, we predict that other LR gene products play a supportive role during life-long latency in cattle. FAU - Jones, Clinton AU - Jones C AD - School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, RM 234, Morisson Life Science Center, Lincoln, NE 68583, USA. cjones@unlnotes.unl.edu FAU - da Silva, Leticia Frizzo AU - da Silva LF FAU - Sinani, Devis AU - Sinani D LA - eng GR - P30 GM103509/GM/NIGMS NIH HHS/United States GR - 1 T32AIO60547/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20111203 PL - United States TA - J Neurovirol JT - Journal of neurovirology JID - 9508123 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Transcription Factors) RN - 0 (Viral Proteins) RN - 0 (latency-related protein, Bovine herpesvirus 1) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Adrenal Cortex Hormones/pharmacology MH - Animals MH - Apoptosis/drug effects MH - Cattle MH - Cattle Diseases/drug therapy/*virology MH - Dexamethasone/pharmacology MH - *Gene Expression Regulation, Viral MH - Herpesviridae Infections/drug therapy/*veterinary/virology MH - Herpesvirus 1, Bovine/*genetics MH - Mutation MH - Promoter Regions, Genetic MH - Sensory Receptor Cells/virology MH - Transcription Factors/genetics/metabolism MH - Transcription, Genetic MH - Trigeminal Ganglion/virology MH - Viral Proteins/genetics/*metabolism MH - Virus Activation/drug effects MH - Virus Latency/*physiology EDAT- 2011/12/06 06:00 MHDA- 2013/02/14 06:00 CRDT- 2011/12/06 06:00 PHST- 2011/08/30 00:00 [received] PHST- 2011/11/06 00:00 [accepted] PHST- 2011/11/02 00:00 [revised] PHST- 2011/12/06 06:00 [entrez] PHST- 2011/12/06 06:00 [pubmed] PHST- 2013/02/14 06:00 [medline] AID - 10.1007/s13365-011-0060-3 [doi] PST - ppublish SO - J Neurovirol. 2011 Dec;17(6):535-45. doi: 10.1007/s13365-011-0060-3. Epub 2011 Dec 3.