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Herpes simplex virus 1 pUL34 plays a critical role in cell-to-cell spread of virus in addition to its role in virus replication.

Department of Microbiology, The University of Iowa, 3-432 Bowen Science Building, Iowa City, IA 52242, USA.
Journal of Virology (Impact Factor: 4.65). 07/2011; 85(14):7203-15. DOI: 10.1128/JVI.00262-11
Source: PubMed

ABSTRACT Herpes simplex virus (HSV) pUL34 plays a critical role in virus replication by mediating egress of nucleocapsids 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 cell-to-cell spread and trafficking of gE. Virion release to the extracellular medium is not affected by the Y68A mutation, indicating that the mutation specifically inhibits cell-to-cell 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 cell-to-cell 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.

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