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J Virol. 2015 Aug;89(16):8444-52. doi: 10.1128/JVI.01143-15. Epub 2015 Jun 3.

The Torsin Activator LULL1 Is Required for Efficient Growth of Herpes Simplex Virus 1.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA christian.schlieker@yale.edu.

Abstract

TorsinA is a membrane-tethered AAA+ ATPase implicated in nuclear envelope dynamics as well as the nuclear egress of herpes simplex virus 1 (HSV-1). The activity of TorsinA and the related ATPase TorsinB strictly depends on LAP1 and LULL1, type II transmembrane proteins that are integral parts of the Torsin/cofactor AAA ring, forming a composite, membrane-spanning assembly. Here, we use CRISPR/Cas9-mediated genome engineering to create single- and double knockout (KO) cell lines of TorA and TorB as well as their activators, LAP1 and LULL1, to investigate the effect on HSV-1 production. Consistent with LULL1 being the more potent Torsin activator, a LULL1 KO reduces HSV-1 growth by one order of magnitude, while the deletion of other components of the Torsin system in combination causes subtle defects. Notably, LULL1 deficiency leads to a 10-fold decrease in the number of viral genomes per host cell without affecting viral protein production, allowing us to tentatively assign LULL1 to an unexpected role that precedes HSV-1 nuclear egress.

IMPORTANCE:

In this study, we conduct the first comprehensive genetic and phenotypic analysis of the Torsin/cofactor system in the context of HSV-1 infection, establishing LULL1 as the most important component of the Torsin system with respect to viral production.

PMID:
26041288
PMCID:
PMC4524217
DOI:
10.1128/JVI.01143-15
[Indexed for MEDLINE]
Free PMC Article

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