PMID- 16987965 OWN - NLM STAT- MEDLINE DCOM- 20070212 LR - 20240413 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 81 IP - 1 DP - 2007 Jan TI - A protein encoded by the bovine herpesvirus 1 latency-related gene interacts with specific cellular regulatory proteins, including CCAAT enhancer binding protein alpha. PG - 59-67 AB - Following acute infection, bovine herpesvirus 1 establishes latency in sensory neurons of trigeminal ganglia (TG). Reactivation from latency occurs periodically, resulting in the shedding of infectious virus. The latency-related (LR) RNA is abundantly expressed in TG of latently infected calves, and the expression of LR proteins is necessary for dexamethasone-induced reactivation from latency. Previously published studies also identified an alternatively spliced LR transcript which is abundantly expressed in TG at 7 days after infection and has the potential to encode a novel LR fusion protein. Seven days after infection is when extensive viral gene expression is extinguished in TG and latency is established, suggesting that LR gene products influence the establishment of latency. In this study, we used a bacterial two-hybrid assay to identify cellular proteins that interact with the novel LR fusion protein. The LR fusion protein interacts with two proteins that can induce apoptosis (Bid and Cdc42) and with CCAAT enhancer binding protein alpha (C/EBP-alpha). Additional studies confirmed that the LR fusion protein interacts with human or insect C/EBP-alpha. C/EBP-alpha protein expression is induced in TG neurons of infected calves and after dexamethasone-induced reactivation from latency. Wild-type C/EBP-alpha, but not a DNA binding mutant of C/EBP-alpha, enhances plaque formation in bovine cells. We hypothesize that interactions between the LR fusion protein and C/EBP-alpha promote the establishment of latency. FAU - Meyer, Florencia AU - Meyer F AD - Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA. FAU - Perez, Sandra AU - Perez S FAU - Geiser, Vicki AU - Geiser V FAU - Sintek, Mark AU - Sintek M FAU - Inman, Melissa AU - Inman M FAU - Jones, Clinton AU - Jones C LA - eng GR - P20 RR015635/RR/NCRR NIH HHS/United States GR - T32 AI060547/AI/NIAID NIH HHS/United States GR - 1P20RR15635/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20060920 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 0 (Drosophila Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Viral Proteins) RN - 0 (latency-related protein, Bovine herpesvirus 1) SB - IM MH - Animals MH - CCAAT-Enhancer-Binding Protein-alpha/*metabolism MH - Cattle MH - Cells, Cultured MH - Drosophila Proteins/metabolism MH - Drosophila melanogaster MH - Gene Expression Regulation, Viral MH - Herpesvirus 1, Bovine/*genetics/metabolism/physiology MH - Humans MH - Mutation MH - Recombinant Fusion Proteins/genetics/metabolism MH - Trigeminal Ganglion/metabolism/virology MH - Two-Hybrid System Techniques MH - Viral Proteins/genetics/*metabolism MH - Virus Latency/genetics/*physiology PMC - PMC1797275 EDAT- 2006/09/22 09:00 MHDA- 2007/02/13 09:00 PMCR- 2007/05/01 CRDT- 2006/09/22 09:00 PHST- 2006/09/22 09:00 [pubmed] PHST- 2007/02/13 09:00 [medline] PHST- 2006/09/22 09:00 [entrez] PHST- 2007/05/01 00:00 [pmc-release] AID - JVI.01171-06 [pii] AID - 1171-06 [pii] AID - 10.1128/JVI.01171-06 [doi] PST - ppublish SO - J Virol. 2007 Jan;81(1):59-67. doi: 10.1128/JVI.01171-06. Epub 2006 Sep 20.