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
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
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DOI：
10.1099/vir.0.19421-0
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发表时间：
2003-11-01
影响因子：
3.8
通讯作者：
Perng, GC
中科院分区：
文献类型：
--
作者：
Mott, KR;Osorio, N;Perng, GC
在单纯疱疹病毒（HSV）-1的神经潜伏期，潜伏相关转录本（LAT）是唯一容易检测到的病毒基因。LAT是动物模型中高水平再激活表型所必需的。LAT的抗凋亡活性最近被我们的小组证明，并提出LAT的抗凋亡功能参与增强再激活表型。最近，使用嵌合病毒CJLAT，显示通过将牛疱疹病毒（BHV）-1潜伏相关（LR）基因插入到该HSV-1 LAT缺失突变体的LAT基因座中，LAT（-）突变体dLAT 2903的再活化表型可以恢复到野生型水平。虽然LR基因的转录，如LAT，抑制细胞凋亡，LR似乎是多功能的。为了研究LR基因的抗凋亡功能是否负责恢复高再活化表型，将突变的BHV-1 LR基因插入HSV-1的LAT基因座中，产生嵌合病毒CJLATMut。该突变由刚好在第一个LR开放阅读框（ORF 2）的ATG之后插入的三个终止密码子组成。在质粒中;而在BHV-1突变体中，这种突变消除了LR基因的抗凋亡活性，强烈表明ORF 2编码负责LR抗凋亡活性的蛋白。在兔和小鼠中，CJLATMut病毒的再活化显著低于野生型McKrae病毒（分别为P=0.0001和P=0.0003）和含有野生型LR代替LAT的CJLAT病毒（P
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