Molecular mechanism of human herpesvirus 6 latent infector

人巨细胞病毒（CMV）是免疫功能低下个体和新生儿的重要病原体。人类疱疹病毒6型（humanherpesvirus 6，HHV-6）是一种可引起潜发性皮疹的病原体。这两种病毒属于b-疱疹病毒亚科。潜伏期是所有疱疹病毒的一个标志，对b型疱疹病毒的了解仍然很少。我们调查的维护和表达的病毒基因组在实验性潜伏感染使用粒细胞-巨噬细胞祖细胞（GM-Ps）的CMV和单核细胞/巨噬细胞的HHV-6。感染巨细胞病毒后，人GM-Ps携带病毒基因组，但不能支持生产性复制。为了更好地了解b型疱疹病毒潜伏期，我们研究了潜伏期系统中病毒基因的表达程度，发现了两类新的CMV潜伏期相关转录本（CLTs）和HHV-6潜伏期转录本（HHV-6LT）。我们表征了这些转录物，并且可以在来自健康CMV血清阳性成人的BM抽吸物和来自健康个体的HHV-6LT中检测到CLT。在CMV和HHV-6的情况下，病毒转录物都来自包含主要调控基因位点的区域;然而，它们的结构与生产期转录物显著不同。在CMV的情况下，这些转录本具有编码新的94和152 aa蛋白的潜力。在HHV-6中编码了新的99 aa、279 aa、91 aa和160 aa蛋白。因此，CMV和HHV-6的潜伏感染伴随着潜伏相关转录物的存在和免疫原性蛋白的表达。总之，这些结果表明，骨髓来源的髓系祖细胞是CMV潜伏期的重要天然部位，外周血来源的单核细胞/巨噬细胞对维持HHV-6潜伏期很重要。

Human cytomegalovirus (CMV) is a significant pathogen in immunocompromised individuals and neonates. Human herpesvirus 6 (HHV-6) is a causative agent of exanthem subitum. These two virusues belong to b-herpesvirus subfamily. Latency, a hallmark of all herpesvirus, remains poorly understood for b-herpesvirus. We investigate maintenance and expression of the viral genome in an experimental latent infection using granulocyte-macrophage progenitors (GM-Ps) for CMV and monocytes/macrophages for HHV-6. Following infection with cytomegalovirus, human GM-Ps carry the viral genome but fail to support productive replication. HHV-6 maintein its genome in human monocytes/macrophages.To better understand b-herpesvirus latency, we investigate the extent of viral gene expression in our latency system and found two novel classes of CMV latency associated transcripts (CLTs) and HHV-6 latency transcript (HHV-6LT). We characterize these transcripts and CLTs can be detected in BM aspirates from healthy CMV seropositive adults and HHV-6LT from healthy individuals. Both in the case of CMV and HHV-6, viral transcripts arise from a region encompassing the major regulatory gene locus ; however, their structure differs significantly from productive phase transcripts. In the case of CMV, these transcripts have the potential to encode novel 94 and 152aa proteins. In HHV-6 novel 99aa, 279aa, 91aa and 160aa proteins are encorded. Thus, latent infection by CMV and HHV-6 is accompanied by the presence of latency-associated transcripts and expression of immunogenic proteins. Overall, these results suggest that bone marrow-derived myeloid progenitors are an important natural site of CMV latency and peripheral blood derived monocytes/macrophages is important to maintein HHV-6 latency.