Cloning and initial characterization of an alternatively spliced transcript encoded by the bovine herpes virus 1 latency-related gene

Bovine herpesvirus 1 (BHV-1) establishes latency in trigeminal ganglionic sensory neurons of infected cattle. The latency-related (LR) RNA is the only abundantly expressed viral transcript in sensory neurons of latently infected calves. Wild-type expression of LR gene products is required for the latency-reactivation cycle in calves. LR RNA is alternatively spliced in trigeminal ganglia (TG) after infection of calves, suggesting that these alternatively spliced transcripts encode novel factors that regulate specific steps during latency. To begin testing whether these alternatively spliced transcripts have novel functions, the authors cloned a full-length cDNA identified in TG of calves at 7 days post infection (dpi) and compared the functions of this cDNA to the intact LR gene. As a result of splicing, the 7 dpi cDNA contains a novel open reading (ORF) comprised of OFR-2 fused to ORF-1. Overexpression of the 7 dpi cDNA inhibited the BHV-1 immediate-early transcription unit 1 (IEtu1) promoter and the herpes simplex virus type 1 ICP0 promoter. Conversely, the 7 dpi cDNA stimulated the LR promoter in transiently transfected cells. A plasmid containing the LR gene had little effect on IEtu1 or LR promoter activity, indicating that the 7 dpi cDNA has novel functions.