title: Influenza virus subpopulations: interferon induction-suppressing particles require expression of NS1 and act globally in cells; UV irradiation of interferon-inducing particles blocks global shut-off and enhances interferon production.
abstract: Influenza virus populations contain several subpopulations of noninfectious biologically active particles that are measured by the unique phenotypes they express. Two of these subpopulations were studied: (1) interferon (IFN)-inducing particles (IFP) and (2) IFN induction-suppressing particles (ISP). ISP are dominant in cells coinfected with one or more IFP; they completely suppress IFN production in cells otherwise programmed to induce it. Influenza virus ISP were shown to act in host cells in a nonspecific and global manner, suppressing IFN induction independent of the family of viruses serving as IFN inducers. ISP must be present within the first 3 h of coinfection with IFP to be maximally effective; by 7 hpi IFN induction/production is refractory to the action of superinfecting ISP. UV target and thermal inactivation analyses revealed that ISP activity was dependent solely on the expression of the NS gene. Low doses of UV radiation enhanced by ∼10-fold the already high IFN-inducing capacity of a virus that expressed truncated NS1. There was no change in the number of IFP, implying that the production of IFN/cell had increased. We postulated that preventing degradation of cellular RNA pol II by viral polymerase prolonged the transcription of cellular mRNA, including IFN mRNA, to enhance the IFN-inducing capacity of the cell without any increase in the number of IFP. These studies point to the dueling roles of IFP and ISP in modulating IFN induction/production, the former activity being critical to the efficacy of live attenuated influenza vaccines.
authors.affiliation: Department of Molecular and Cell Biology, Virus and Interferon Research Laboratory, University of Connecticut, Storrs, CT 06269, 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; D002642:Chick Embryo; D007369:Interferon Inducers / Q000494:pharmacology*; D007372:Interferons / Q000096:biosynthesis*; D009975:Orthomyxoviridae / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014771:Virion / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects
chemical_list: C085820:INS1 protein, influenza virus; D007369:Interferon Inducers; D017361:Viral Nonstructural Proteins; D007372:Interferons