Reactivation phenotype in rabbits of a herpes simplex virus type 1 mutant containing an unrelated antiapoptosis gene in place of latency-associated transcript
Reactivation phenotype in rabbits of a herpes simplex virus type 1 mutant containing an unrelated antiapoptosis gene in place of latency-associated transcript
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DOI：
10.1080/13550280601164333
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Wechsler, Steven L.
中科院分区：
文献类型：
--
作者：
Jin, Ling;Perng, Guey-Chuen;Wechsler, Steven L.
潜伏相关转录本（LAT）显著增强单纯疱疹病毒1型（HSV-1）的自发再活化表型。土地增值税实现这一点的机制一直难以捉摸。为了确定是否涉及LAT的抗凋亡活性，作者使用兔眼模型来分析HSV-1突变体的自发再激活表型，其中LAT被不相关的抗凋亡基因取代。该病毒dLAT-cpIAP含有杆状病毒凋亡抑制蛋白基因（cpIAP）的开放阅读框，代替LAT，受LAT启动子控制。作者在此报道，在兔眼感染模型中，dLAT-cpIAP具有与野生型病毒相似的自发再活化表型，且显著高于LAT（-）病毒。这与他们先前使用小鼠三叉神经节外植体诱导的再激活模型的发现一致。LAT（以及dLAT-cpIAP，cpIAP）是否通过在潜伏期建立、潜伏期维持或潜伏期再激活期间或在两个或多个这些期间发挥作用来增强自发再激活表型，仍有待确定。无论如何，本研究的结果强烈支持LAT的抗凋亡活性是增强HSV-1自发再激活表型的主要功能的假设。
Latency-associated transcript ( LAT) significantly enhances the spontaneous reactivation phenotype of herpes simplex virus type 1 ( HSV-1). The mechanism by which LAT accomplishes this has been elusive. To determine if LAT's antiapoptosis activity is involved, the authors used a rabbit eye model to analyze the spontaneous reactivation phenotype of an HSV-1 mutant in which LAT was replaced by an unrelated antiapoptosis gene. This virus, dLAT-cpIAP, contains the open reading frame of the baculovirus inhibitor of apoptosis protein gene ( cpIAP) in place of LAT, under control of the LAT promoter. The authors report here that in a rabbit ocular model of infection, dLAT-cpIAP had a spontaneous reactivation phenotype similar to wild-type virus and significantly higher than LAT(-) viruses. This was consistent with their previous findings using the mouse trigeminal ganglia explant - induced reactivation model. Whether LAT ( and in the case of dLAT-cpIAP, cpIAP) enhances the spontaneous reactivation phenotype by functioning during establishment of latency, maintenance of latency, or reactivation from latency, or during two or more of these periods, remains to be determined. Regardless, the results presented in this study strongly support the hypothesis that LAT's antiapoptosis activity is the dominant function that enhances HSV-1's spontaneous reactivation phenotype.