Herpes Simplex Virus 1 pUL34 Plays a Critical Role in Cell-to-Cell Spread of Virus in Addition to Its Role in Virus Replication
Herpes Simplex Virus 1 pUL34 Plays a Critical Role in Cell-to-Cell Spread of Virus in Addition to Its Role in Virus Replication
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DOI：
10.1128/jvi.00262-11
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发表时间：
2011-07-01
影响因子：
5.4
通讯作者：
Roller, Richard J.
中科院分区：
文献类型：
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作者：
Haugo, Alison C.;Szpara, Moriah L.;Roller, Richard J.
单纯疱疹病毒 (HSV) pUL34 通过介导核衣壳从受感染的细胞核中流出，在病毒复制中发挥关键作用。我们发现了 pUL34 (Y68A) 中的一个突变，该突变会导致病毒复制出现重大缺陷并导致核出口受损，同时也会严重抑制细胞间的传播和 gE 的运输。病毒颗粒向细胞外介质的释放不受Y68A突变的影响，表明该突变特异性抑制细胞间的传播。我们分离了 Y68A 噬菌斑形成缺陷的基因外抑制因子，并通过高通量 Illumina 测序和基于 PCR 的筛选相结合来绘制它们的图谱。我们发现抑制与 US9 基因中的无义突变高度相关，US9 基因在 HSV-1 在神经元中的细胞间传播中发挥着关键作用。仅 US9 突变不足以抑制 Y68A 传播表型，表明多种病毒因素可能发挥作用。
Herpes simplex virus (HSV) pUL34 plays a critical role in virus replication by mediating egress of nucleo-capsids from the infected cell nucleus. We have identified a mutation in pUL34 (Y68A) that produces a major defect in virus replication and impaired nuclear egress but also profoundly inhibits celltocell spread and trafficking of gE. Virion release to the extracellular medium is not affected by the Y68A mutation, indicating that the mutation specifically inhibits celltocell spread. We isolated extragenic suppressors of the Y68A plaque formation defect and mapped them by a combination of high-throughput Illumina sequencing and PCR-based screening. We found that suppression is highly correlated with a nonsense mutation in the US9 gene, which plays a critical role in celltocell spread of HSV-1 in neurons. The US9 mutation alone is not sufficient to suppress the Y68A spread phenotype, indicating a likely role for multiple viral factors.