The ATP-Dependent RNA Helicase DDX3X Modulates Herpes Simplex Virus 1 Gene Expression.
The human protein DDX3X is a DEAD box ATP-dependent RNA helicase that regulates transcription, mRNA maturation, and mRNA export and translation. DDX3X concomitantly modulates the replication of several RNA viruses and promotes innate immunity. We previously showed that herpes simplex virus 1 (HSV-1), a human DNA virus, incorporates DDX3X into its mature particles and that DDX3X is required for optimal HSV-1 infectivity. Here, we show that viral gene expression, replication, and propagation depend on optimal DDX3X protein levels. Surprisingly, DDX3X from incoming viral particles was not required for the early stages of the HSV-1 infection, but, rather, the protein controlled the assembly of new viral particles. This was independent of the previously reported ability of DDX3X to stimulate interferon type I production. Instead, both the lack and overexpression of DDX3X disturbed viral gene transcription and thus subsequent genome replication. This suggests that in addition to its effect on RNA viruses, DDX3X impacts DNA viruses such as HSV-1 by an interferon-independent pathway.IMPORTANCEViruses interact with a variety of cellular proteins to complete their life cycle. Among them is DDX3X, an RNA helicase that participates in most aspects of RNA biology, including transcription, splicing, nuclear export, and translation. Several RNA viruses and a limited number of DNA viruses are known to manipulate DDX3X for their own benefit. In contrast, DDX3X is also known to promote interferon production to limit viral propagation. Here, we show that DDX3X, which we previously identified in mature HSV-1 virions, stimulates HSV-1 gene expression and, consequently, virion assembly by a process that is independent of its ability to promote the interferon pathway.
Department of Pathology and Cell biology, University of Montreal, Montreal, Quebec, Canada.
Bita
B
Khadivjam
Department of Pathology and Cell biology, University of Montreal, Montreal, Quebec, Canada.
Camille
C
Stegen
Department of Pathology and Cell biology, University of Montreal, Montreal, Quebec, Canada.
Marc-Aurèle
MA
Hogue-Racine
Department of Pathology and Cell biology, University of Montreal, Montreal, Quebec, Canada.
Nabil
N
El Bilali
Institute of Virology, Hannover Medical School, Hannover, Germany.
Katinka
K
Döhner
Institute of Virology, Hannover Medical School, Hannover, Germany.
Beate
B
Sodeik
Department of Pathology and Cell biology, University of Montreal, Montreal, Quebec, Canada roger.lippe@umontreal.ca.
Roger
R
Lippé
D000818:Animals; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D019065:Virus Assembly; D014779:Virus Replication
C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases
DDX3X; DNA virus; RNA virus; helicase; herpes; herpes simplex virus; host-pathogen interaction; host-pathogen interactions; interferon; transcriptional regulation; translational control