title: Analysis of virion-incorporated host proteins required for herpes simplex virus type 1 infection through a RNA interference screen.
abstract: Viruses are strictly dependent on cells to propagate and many incorporate host proteins in their viral particles, but the significance of this incorporation is poorly understood. Recently, we performed the first comprehensive characterization of the mature herpes simplex virus type 1 (HSV-1) in which up to 49 distinct cellular proteins were identified by mass spectrometry. In the present study, we sought to identify if these cellular factors are relevant for the HSV-1 life cycle. To this end, we performed a small interfering RNA functional screen and found that 15 of these host proteins altered HSV-1 proliferation in cell culture, without any significant effect on cell viability. Moreover, the siRNA used had no negative consequences for Adenovirus type 5 propagation (with one exception) indicating that the modulation was specific for HSV-1 and not merely due to unhealthy cells. The positive host proteins include several Rab GTPases and other intracellular transport components as well as proteins involved in signal transduction, gene regulation and immunity. Remarkably, in most cases when virions were depleted for one of the above proteins, they replicated more poorly in subsequent infections in wild type cells. This highlights for the first time that both the cellular and virion-associated pools of many of these proteins actively contribute to viral propagation. Altogether, these findings underscore the power and biological relevance of combining proteomics and RNA interference to identify novel host-pathogen interactions.
authors.affiliation: Department of Pathology and Cell Biology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Camille
authors.initials: C
authors.lastname: Stegen
authors.forename: Yordanka
authors.initials: Y
authors.lastname: Yakova
authors.forename: Daniel
authors.initials: D
authors.lastname: Henaff
authors.forename: Julien
authors.initials: J
authors.lastname: Nadjar
authors.forename: Johanne
authors.initials: J
authors.lastname: Duron
authors.forename: Roger
authors.initials: R
authors.lastname: Lippé
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000502:physiology*; D013058:Mass Spectrometry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism; D014771:Virion / Q000378:metabolism*; D014779:Virus Replication; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins; D020691:rab GTP-Binding Proteins