title: Increased virus replication in mammalian cells by blocking intracellular innate defense responses.
abstract: The mammalian innate immune system senses viral infection by recognizing viral signatures and activates potent antiviral responses. Besides the interferon (IFN) response, there is accumulating evidence that RNA silencing or RNA interference (RNAi) serves as an antiviral mechanism in mammalian cells. Mammalian viruses encode IFN antagonists to counteract the IFN response in infected cells. A number of IFN antagonists are also capable of blocking RNAi in infected cells and therefore serve as RNA-silencing suppressors. Virus replication in infected cells is restricted by these innate antiviral mechanisms, which may kick in earlier than the viral antagonistic or suppressor protein can accumulate. The yield of virus vaccines and viral gene delivery vectors produced in mammalian producer cells may therefore be suboptimal. To investigate whether blocking of the innate antiviral responses in mammalian cells leads to increased viral vector production, we expressed a number of immunity suppressors derived from plant and mammalian viruses in human cells. We measured that the yield of infectious human immunodeficiency virus-1 particles produced in these cells was increased 5- to 10-fold. In addition, the production of lentiviral and adenoviral vector particles was increased 5- to 10-fold, whereas Sindbis virus particle production was increased approximately 100-fold. These results can be employed for improving the production of viral gene transfer vectors and viral vaccine strains.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands. w.g.devries@amc.nl
authors.forename: W
authors.initials: W
authors.lastname: de Vries
authors.forename: J
authors.initials: J
authors.lastname: Haasnoot
authors.forename: J
authors.initials: J
authors.lastname: van der Velden
authors.forename: T
authors.initials: T
authors.lastname: van Montfort
authors.forename: F
authors.initials: F
authors.lastname: Zorgdrager
authors.forename: W
authors.initials: W
authors.lastname: Paxton
authors.forename: M
authors.initials: M
authors.lastname: Cornelissen
authors.forename: F
authors.initials: F
authors.lastname: van Kuppeveld
authors.forename: P
authors.initials: P
authors.lastname: de Haan
authors.forename: B
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D002417:Cattle; D002460:Cell Line; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000037:antagonists & inhibitors*; D034622:RNA Interference; D034743:RNA-Induced Silencing Complex; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012845:Sindbis Virus / Q000502:physiology; D014162:Transfection / Q000379:methods; D014765:Viral Vaccines / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*; D014779:Virus Replication
chemical_list: D034743:RNA-Induced Silencing Complex; D014765:Viral Vaccines; D007372:Interferons