Tang Shuang, Bertke Andrea S, Patel Amita, Wang Kening, Cohen Jeffrey I, Krause Philip R
Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10931-6. doi: 10.1073/pnas.0801845105. Epub 2008 Aug 4.
Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression.
潜伏期相关转录本（LAT）序列调节单纯疱疹病毒（HSV）在感觉神经元中的潜伏和再激活。我们在体外转染和感染的细胞以及体内豚鼠急性和潜伏感染的神经节中发现了一种与HSV-2 LAT相关的微小RNA（miRNA），命名为miR-I。miR-I也在潜伏感染HSV-2的人骶背根神经节中表达。在体内感染的感觉神经节中，miR-I在LAT启动子的调控下表达。我们还在与miR-I相似的位置预测并鉴定了一种HSV-1 LAT外显子2病毒miRNA，这意味着在这些密切相关的病毒中存在一种保守机制。在转染和感染的细胞中，miR-I降低关键病毒神经毒力因子ICP34.5的表达。我们推测，miR-I可能通过作为ICP34.5表达的分子开关来调节病毒在周围神经系统中的感染结果。
