title: Induction of dendritic cell production of type I and type III interferons by wild-type and vaccine strains of measles virus: role of defective interfering RNAs.
abstract: The innate immune response to viral infection frequently includes induction of type I interferons (IFN), but many viruses have evolved ways to block this response and increase virulence. In vitro studies of IFN production after infection of susceptible cells with measles virus (MeV) have often reported greater IFN synthesis after infection with vaccine than with wild-type strains of MeV. However, the possible presence in laboratory virus stocks of 5' copy-back defective interfering (DI) RNAs that induce IFN independent of the standard virus has frequently confounded interpretation of data from these studies. To further investigate MeV strain-dependent differences in IFN induction and the role of DI RNAs, monocyte-derived dendritic cells (moDCs) were infected with the wild-type Bilthoven strain and the vaccine Edmonston-Zagreb strain with and without DI RNAs. Production of type I IFN, type III IFN, and the interferon-stimulated genes (ISGs) Mx and ISG56 by infected cells was assessed with a flow cytometry-based IFN bioassay, quantitative reverse transcriptase PCR (RT-PCR), and immunoassays. Bilthoven infected moDCs less efficiently than Edmonston-Zagreb. Presence of DI RNAs in vaccine stocks resulted in greater maturation of moDCs, inhibition of virus replication, and induction of higher levels of IFN and ISGs. Production of type I IFN, type III IFN, and ISG mRNA and protein was determined by both the level of infection and the presence of DI RNAs. At the same levels of infection and in the absence of DI RNA, IFN induction was similar between wild-type and vaccine strains of MeV.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Rupak
authors.initials: R
authors.lastname: Shivakoti
authors.forename: Martina
authors.initials: M
authors.lastname: Siwek
authors.forename: Debra
authors.initials: D
authors.lastname: Hauer
authors.forename: Kimberly L W
authors.initials: KL
authors.lastname: Schultz
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D007372:Interferons / Q000096:biosynthesis* / Q000276:immunology; D008459:Measles virus / Q000276:immunology*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics*; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C484290:IFIT1 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014765:Viral Vaccines; D007372:Interferons