A replication-defective gammaherpesvirus efficiently establishes long-term latency in macrophages but not in B cells in vivo.
A replication-defective gammaherpesvirus efficiently establishes long-term latency in macrophages but not in B cells in vivo.
复制标题
复制缺陷型伽马疱疹病毒可有效地在巨噬细胞中建立长期潜伏期，但不能在体内 B 细胞中建立长期潜伏期。
DOI：
10.1128/jvi.00186-08
复制
发表时间：
2008
影响因子：
5.4
通讯作者：
Tibbetts,ScottA
中科院分区：
文献类型：
--
作者：
Li,Haiyan;Ikuta,Kazufumi;Sixbey,JohnW;Tibbetts,ScottA
小鼠γ -疱疹病毒68 （γ - hv68或MHV68）与人类γ -疱疹病毒eb病毒（EBV）和卡波西肉瘤相关疱疹病毒（KSHV）具有遗传相关性，为体内研究病毒-宿主关系提供了一个有用的系统。为了开始解决关于伽马疱疹病毒潜伏期建立机制的基本问题，我们之前生成了一个复制缺陷的γHV68，缺乏由yorf6编码的单链DNA结合蛋白的表达。在这里提出的工作中，我们证明了这种突变病毒在体内建立了长期感染，其分子潜伏期与野生型病毒相同。因此，尽管没有裂解复制的急性期，突变病毒建立了慢性感染，其中病毒基因组(i)维持为发作体，（ii）表达与潜伏期相关的基因，但不表达与裂解复制相关的基因。从感染复制缺陷病毒的小鼠中纯化的巨噬细胞以几乎与野生型γHV68相同的频率携带病毒基因组；然而，在没有裂解复制的情况下，B细胞携带病毒基因组的频率大大降低。因此，这种复制缺陷的γ疱疹病毒在巨噬细胞中有效地建立了体内感染，在分子上与野生型病毒潜伏期没有区别。这些数据表明，在B细胞潜伏感染的建立或维持中，溶酶复制或再激活起着关键作用。
Murine gammaherpesvirus 68 (γHV68 or MHV68) is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), providing a useful system for in vivo studies of the virus-host relationship. To begin to address fundamental questions about the mechanisms of the establishment of gammaherpesvirus latency, we previously generated a replication-defective γHV68 lacking the expression of the single-stranded DNA binding protein encoded byorf6. In work presented here, we demonstrate that this mutant virus established a long-term infection in vivo that was molecularly identical to wild-type virus latency. Thus, despite the absence of an acute phase of lytic replication, the mutant virus established a chronic infection in which the viral genome (i) was maintained as an episome and (ii) expressed latency-associated, but not lytic replication-associated, genes. Macrophages purified from mice infected with the replication-defective virus harbored viral genome at a frequency that was nearly identical to that of wild-type γHV68; however, the frequency of B cells harboring viral genome was greatly reduced in the absence of lytic replication. Thus, this replication-defective gammaherpesvirus efficiently established in vivo infection in macrophages that was molecularly indistinguishable from wild-type virus latency. These data point to a critical role for lytic replication or reactivation in the establishment or maintenance of latent infection in B cells.