title: Influenza virus: a single noninfectious interferon induction-suppressing particle blocks expression of interferon-inducing particles.
abstract: The interferon (IFN)-inducing capacity of influenza virus plays a significant role in the efficacy of candidate live attenuated influenza vaccines (LAIVs). IFN is induced by a subpopulation of noninfectious biologically active particles (niBAPs) that can be defined and quantified as IFN-inducing particles (IFPs). When chicken embryonic cells were infected with increasing multiplicities of IFP (m(ifp)), the amount of IFN produced was that expected from a Poisson distribution of cells infected with ≥1 IFP. Problematically, some isolates of influenza virus induced less IFN than expected at higher m(ifp). We postulated that these stocks contained another subpopulation of niBAP, IFN induction-suppressing particles (ISPs). A single ISP was assumed capable of preventing IFN production completely in cells coinfected with IFP. Virus stocks were reconstructed to contain a wide range of ratios of IFP:ISP and used to generate IFN-induction dose-response curves. The deviation of the observed yields of IFN from those expected if the virus stock consisted only of IFP fits well the results expected from a formulation of the Poisson distribution that provides the fraction of IFP-infected cells expected to become coinfected with ISP, and hence not yield IFN, as the ratio IFP:ISP decreases. The ideal LAIV might be thought to contain little or no ISP so as to maximize IFN production; however, the most effective LAIV appear to regulate the production of IFN. Thus, it is possible that an optimal ratio of IFP:ISP may exist to produce more effective LAIV, an event that may sometimes occur in nature, or be reconstructed.
authors.affiliation: Laboratory for Virus and Interferon Research, Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Malinoski
authors.forename: Philip I
authors.initials: PI
authors.lastname: Marcus
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004306:Dose-Response Relationship, Immunologic; D007252:Influenza Vaccines; D007369:Interferon Inducers; D007372:Interferons / Q000096:biosynthesis*; D009975:Orthomyxoviridae / Q000502:physiology*; D014613:Vaccines, Attenuated; D014771:Virion
chemical_list: D007252:Influenza Vaccines; D007369:Interferon Inducers; D014613:Vaccines, Attenuated; D007372:Interferons