An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor
Shuang Tang*, Andrea S. Bertke*, Amita Patel*, Kening Wang†, Jeffrey I. Cohen†, and Philip R. Krause*,‡
+Author Affiliations
*Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892; and
†Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892
Edited by Thomas E. Shenk, Princeton University, Princeton, NJ, and approved June 3, 2008 (received for review March 6, 2008)
Abstract
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.
根据一份研究报告，一种新发现的化合物可能对生殖器疱疹的潜伏和再激活具有关键作用。Philip Krause及其同事在专门搜索了单纯疱疹病毒2型（HSV-2）遗传结构中的小分子RNA之后，发现了一段称为“miR-I”的RNA序列。单纯疱疹病毒会导致生殖器疱疹。这组科学家发现，尽管这种疱疹病毒在两次暴发之间处于休眠状态，它的基因组几乎不会产生什么，除了潜伏相关转录体（LAT）。LAT含有小段RNA，似乎只有一个功能——阻止这种病毒在神经细胞中复制的“毒力因子”的表达。
一旦这组科学家知道了miR-I的基因序列，他们就能够在被疱疹病毒感染的豚鼠的神经元和被感染的人类的尸检样本中发现高水平表达的这种小分子RNA。由于miR-I位于和HSV2的已知毒力因子相对的病毒DNA链上，这组作者提出了一个假说并用实验进行了验证，即miR-I可能通过起到一种分子开关的作用，影响这种疱疹病原体在宿主体内繁殖的能力，从而调控周围神经系统的病毒感染的结果。
