Evans Andrew G, Moorman Nathaniel J, Willer David O, Speck Samuel H
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta, GA 30329, USA.
Virology. 2006 Jan 20;344(2):520-31. doi: 10.1016/j.virol.2005.08.020. Epub 2005 Sep 26.
Sequence analysis of the murine gamma-herpesvirus 68 (gammaHV68) genome previously identified several open reading frames (ORFs) located at the left end of the viral genome that do not share homology with other known herpesvirus or cellular genes. Here, we show that one of these ORFs, M4, encodes a secreted glycoprotein that influences the establishment of splenic latency at early times post-infection. We generated a mutant virus containing a premature translation termination codon in the M4 ORF (M4.STOP), and demonstrated that this mutant virus replicates in vitro equivalent to wild type and marker rescue (M4.MR) viruses. M4.STOP was also capable of high-titer lytic replication in vivo, but at 16 days post-infection the establishment of latency in the spleen was significantly impaired. The defect in the establishment of splenic latency was apparent following either intranasal or intraperitoneal inoculation. In contrast, the M4.STOP mutant did not exhibit a defect in the establishment of latency in peritoneal cells. These results suggest that M4 mediates an extracellular host-pathogen interaction that impacts the establishment of latent infection in the spleen, but not the peritoneum.
小鼠γ-疱疹病毒68（γHV68）基因组的序列分析先前已鉴定出位于病毒基因组左端的几个开放阅读框（ORF），这些开放阅读框与其他已知的疱疹病毒或细胞基因没有同源性。在此，我们表明这些ORF之一，即M4，编码一种分泌型糖蛋白，该糖蛋白在感染后早期影响脾脏潜伏感染的建立。我们构建了一种在M4 ORF中含有过早翻译终止密码子的突变病毒（M4.STOP），并证明该突变病毒在体外的复制能力与野生型和标记拯救（M4.MR）病毒相当。M4.STOP在体内也能够进行高滴度的裂解复制，但在感染后16天，其在脾脏中潜伏感染的建立受到显著损害。无论是经鼻内还是腹腔内接种，脾脏潜伏感染建立的缺陷都很明显。相比之下，M4.STOP突变体在腹膜细胞潜伏感染的建立方面没有表现出缺陷。这些结果表明，M4介导了一种细胞外宿主-病原体相互作用，这种相互作用影响脾脏而非腹膜中潜伏感染的建立。
