title: Beta interferon and gamma interferon synergize to block viral DNA and virion synthesis in herpes simplex virus-infected cells.
abstract: The capacity of herpes simplex virus type 1 (HSV-1) to replicate in vitro decreases tremendously when animal cell cultures are exposed to ligands of both the alpha/beta interferon (IFN-alpha/beta) receptor and IFN-gamma receptor prior to inoculation with low m.o.i.s of HSV-1. However, the available evidence provides no insight into the possible mechanisms by which co-activation of the IFN-alpha/beta- and IFN-gamma-signalling pathways produces this effect. Therefore, it has not been possible to differentiate between whether these observations represent an important in vitro model of host immunological suppression of HSV-1 infection or an irrelevant laboratory phenomenon. Therefore, the current study was initiated to determine whether co-activation of the host cell's IFN-alpha/beta and IFN-gamma pathways either (i) induced death of HSV-1-infected cells such that virus replication was unable to occur; or (ii) disrupted one or more steps in the process of HSV-1 replication. To this end, multiple steps in HSV-1 infection were compared in populations of Vero cells infected with HSV-1 strain KOS (m.o.i. of 2.5) and exposed to ligands of the IFN-alpha/beta receptor, the IFN-gamma receptor or both. The results demonstrated that IFN-beta and IFN-gamma interact in a synergistic manner to block the efficient synthesis of viral DNA and nucleocapsid formation in HSV-1-infected cells and do so without compromising host-cell viability. It was inferred that IFN-mediated suppression of HSV-1 replication may be a central mechanism by which the host immune system limits the spread of HSV-1 infection in vivo.
authors.affiliation: Department of Microbiology and Immunology, Tulane University Medical School, New Orleans, LA 70112, USA.
authors.forename: Amy T
authors.initials: AT
authors.lastname: Pierce
authors.affiliation: Department of Microbiology and Immunology, Tulane University Medical School, New Orleans, LA 70112, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: DeSalvo
authors.affiliation: Division of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Foster
authors.affiliation: Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Athena
authors.initials: A
authors.lastname: Kosinski
authors.affiliation: Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Weller
authors.affiliation: Department of Veterinary Molecular Biology, Montana State University, 960 Technology Boulevard, Bozeman, MT 59718, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Halford
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D004357:Drug Synergism; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D017471:Receptors, Interferon; D014709:Vero Cells; D014771:Virion / Q000187:drug effects / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D017471:Receptors, Interferon; D016899:Interferon-beta; D007371:Interferon-gamma