title: The orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination.
abstract: Nonliving antiviral vaccines traditionally target proteins expressed at the surface of the virion with the hope of inducing neutralizing antibodies. Orthopoxviruses (OPVs), such as the human smallpox virus and the mouse-equivalent ectromelia virus (ECTV; an agent of mousepox), encode immune response modifiers (IRMs) that can increase virulence by decreasing the host immune response. We show that one of these IRMs, the type I interferon (IFN) binding protein (bp) of ECTV, is essential for ECTV virulence and is a natural target of the antibody response. More strikingly, we demonstrate that immunization with recombinant type I IFN bp protects mice from lethal mousepox. Collectively, our experiments have important implications for our understanding of the role of IRMs in OPV virulence and of type I IFNs in OPV infections. Furthermore, our work provides proof of concept that effective antiviral vaccines can be made to prevent disease by targeting virulence factors as an alternative to the traditional approach that attempts to prevent infection by virus neutralization.
authors.affiliation: Program of Viral Pathogenesis, Division of Basic Science, Fox Chase Cancer Center (FCCC), Philadelphia, PA 19111, USA.
authors.forename: Ren-Huan
authors.initials: RH
authors.lastname: Xu
authors.forename: Matthew
authors.initials: M
authors.lastname: Cohen
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Eric
authors.initials: E
authors.lastname: Lazear
authors.forename: J Charles
authors.initials: JC
authors.lastname: Whitbeck
authors.forename: Roselyn J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: Gary H
authors.initials: GH
authors.lastname: Cohen
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Sigal
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D004481:Ectromelia virus / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity*; D004482:Ectromelia, Infectious / Q000517:prevention & control / Q000821:virology; D005816:Genetic Complementation Test; D007113:Immunity, Innate / Q000276:immunology; D007121:Immunocompetence; D007370:Interferon Type I / Q000276:immunology; D051379:Mice; D016366:Open Reading Frames / Q000235:genetics; D011485:Protein Binding; D017471:Receptors, Interferon / Q000172:deficiency; D011994:Recombinant Proteins; D046509:Tissue Culture Techniques; D014611:Vaccination; D014764:Viral Proteins / Q000276:immunology*; D014774:Virulence
chemical_list: D007370:Interferon Type I; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D014764:Viral Proteins