A protein encoded by the bovine herpesvirus 1 latency-related gene interacts with specific cellular regulatory proteins, including CCAAT enhancer binding protein alpha.
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.
Meyer
Florencia
F
Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA.
Perez
Sandra
S
Geiser
Vicki
V
Sintek
Mark
M
Inman
Melissa
M
Jones
Clinton
C
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D015967:Gene Expression Regulation, Viral; D007242:Herpesvirus 1, Bovine / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000821:virology; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency / Q000235:genetics / Q000502:physiology*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C401822:latency-related protein, Bovine herpesvirus 1