Murine gammaherpesvirus 68 lacking gp150 shows defective virion release but establishes normal latency in vivo
Murine gammaherpesvirus 68 lacking gp150 shows defective virion release but establishes normal latency in vivo
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DOI：
10.1128/jvi.78.10.5103-5112.2004
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发表时间：
2004-05-01
影响因子：
5.4
通讯作者：
Stevenson, PG
中科院分区：
文献类型：
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作者：
De Lima, BD;May, JS;Stevenson, PG
所有γ疱疹病毒编码与爱泼斯坦-巴尔病毒gp 350位置同源的病毒粒子糖蛋白。这些糖蛋白被认为与细胞结合有关，但对它们在整个病毒复制周期中可能发挥的作用知之甚少。我们分析了海洋γ疱疹病毒68（MRV-68）gp 150的贡献，在体外病毒繁殖和宿主体内定植。缺乏gp 150的MHV-68是活的，并显示出与成纤维细胞的正常结合和正常的单周期裂解复制。其感染糖胺聚糖（GAG）缺陷型CHO-K1细胞和NS 0和RAW264.7细胞（仅表达低水平的GAG）的能力反而增加。然而，gp 150缺陷型MHV-68在成纤维细胞单层中的传播较差，无细胞感染性降低，与病毒释放缺陷一致。电子显微镜显示gp 150缺陷病毒粒子聚集在感染细胞质膜上。MHV-68感染的细胞显示表面GAG表达减少，表明gp 150通过使MHV-68感染GAG依赖性，防止病毒体在释放后重新结合感染的细胞。令人惊讶的是，gp 150缺陷型病毒在体内裂解复制中仅表现出短暂的滞后，并建立了正常水平的潜伏期。因此，细胞间病毒传播和潜伏感染细胞的增殖（其中gp 150被阻断）似乎是病毒在感染宿主中繁殖的主要途径。
All gammaherpesviruses encode a virion glycoprotein positionally homologous to Epstein-Barr virus gp350. These glycoproteins are thought to be involved in cell binding, but little is known of the roles they might play in the whole viral replication cycle. We have analyzed the contribution of marine gammaherpesvirus 68 (MRV-68) gp150 to viral propagation in vitro and host colonization in vivo. MHV-68 lacking gp150 was viable and showed normal binding to fibroblasts and normal single-cycle lytic replication. Its capacity to infect glycosaminoglycan (GAG)-deficient CHO-K1 cells and NS0 and RAW264.7 cells, which express only low levels of GAGs, was paradoxically increased. However, gp150-deficient MHV-68 spread poorly through fibroblast monolayers, with reduced cell-free infectivity, consistent with a deficit in virus release. Electron microscopy showed gp150-deficient virions clustered on infected-cell plasma membranes. MHV-68-infected cells showed reduced surface GAG expression, suggesting that gp150 prevented virions from rebinding to infected cells after release by making MHV-68 infection GAG dependent. Surprisingly, gp150-deficient viruses showed only a transient lag in lytic replication in vivo and established normal levels of latency. Cell-to-cell virus spread and the proliferation of latently infected cells, for which gp150 was dispensable, therefore appeared to be the major route of virus propagation in an infected host.