%0 Journal Article %A Mott, Kevin R. %A Osorio, Nelson %A Jin, Ling %A Brick, David J. %A Naito, Julie %A Cooper, Jennifer %A Henderson, Gail %A Inman, Melissa %A Jones, Clinton %A Wechsler, Steven L. %A Perng, Guey-Chuen %T The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant %D 2003 %J Journal of General Virology, %V 84 %N 11 %P 2975-2985 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.19421-0 %I Microbiology Society, %X During neuronal latency of herpes simplex virus (HSV)-1, the latency-associated transcript (LAT) is the only viral gene readily detectable. LAT is required for the high-level reactivation phenotype in animal models. LAT's anti-apoptotic activity was recently demonstrated by our group and it was proposed that LAT's anti-apoptotic function is involved in enhancing the reactivation phenotype. Recently, using chimeric virus CJLAT, it was shown that the reactivation phenotype of LAT− mutant dLAT2903 can be restored to wild-type levels by inserting the bovine herpes virus (BHV)-1 latency-related (LR) gene into the LAT locus of this HSV-1 LAT deletion mutant. Although transcription of the LR gene, like LAT, inhibits apoptosis, LR appears to be multifunctional. To investigate whether the LR gene's anti-apoptotic function was responsible for restoring the high-reactivation phenotype, a mutated BHV-1 LR gene was inserted into the LAT locus of HSV-1 generating the chimeric virus CJLATmut. This mutation consists of three stop codons inserted just after the ATG of the first LR open reading frame (ORF2). In plasmids and in a BHV-1 mutant, this mutation eliminated the LR gene's anti-apoptotic activity, strongly suggesting that ORF2 encodes a protein responsible for LR's anti-apoptotic activity. Reactivation of the CJLATmut virus, in both rabbits and mice, was significantly lower than in wild-type McKrae virus (P=0·0001 and P=0·0003, respectively) and CJLAT virus, containing wild-type LR in place of LAT (P<0·0001) and was similar to LAT− dLAT2903 (P=0·8 and P=0·7, respectively). Thus, disruption of BHV-1 LR ORF2 eliminated the high-reactivation phenotype. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.19421-0