title: Virus growth and antibody responses following respiratory tract infection of ferrets and mice with WT and P/V mutants of the paramyxovirus Simian Virus 5.
abstract: P/V gene substitutions convert the non-cytopathic paramyxovirus Simian Virus 5 (SV5), which is a poor inducer of host cell responses in human tissue culture cells, into a mutant (P/V-CPI-) that induces high levels of apoptosis, interferon (IFN)-beta, and proinflammatory cytokines. However, the effect of SV5-P/V gene mutations on virus growth and adaptive immune responses in animals has not been determined. Here, we used two distinct animal model systems to test the hypothesis that SV5-P/V mutants which are more potent activators of innate responses in tissue culture will also elicit higher antiviral antibody responses. In mouse cells, in vitro studies identified a panel of SV5-P/V mutants that ranged in their ability to limit IFN responses. Intranasal infection of mice with these WT and P/V mutant viruses elicited equivalent anti-SV5 IgG responses at all doses tested, and viral titers recovered from the respiratory tract were indistinguishable. In primary cultures of ferret lung fibroblasts, WT rSV5 and P/V-CPI- viruses had phenotypes similar to those established in human cell lines, including differential induction of IFN secretion, IFN signaling and apoptosis. Intranasal infection of ferrets with a low dose of WT rSV5 elicited approximately 500 fold higher anti-SV5 serum IgG responses compared to the P/V-CPI- mutant, and this correlated with overall higher viral titers for the WT virus in tracheal tissues. There was a dose-dependent increase in antibody response to infection of ferrets with P/V-CPI-, but not with WT rSV5. Together our data indicate that WT rSV5 and P/V mutants can elicit distinct innate and adaptive immunity phenotypes in the ferret animal model system, but not in the mouse system. We present a model for the effect of P/V gene substitutions on SV5 growth and immune responses in vivo.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1064, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Capraro
authors.forename: John B
authors.initials: JB
authors.lastname: Johnson
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Kock
authors.forename: Griffith D
authors.initials: GD
authors.lastname: Parks
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005289:Ferrets; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D007074:Immunoglobulin G / Q000097:blood; D007372:Interferons / Q000096:biosynthesis; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009666:Nose / Q000821:virology; D045402:Parainfluenza Virus 5 / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics*; D017354:Point Mutation; D016601:RNA-Binding Proteins; D019351:Rubulavirus Infections / Q000097:blood* / Q000378:metabolism / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; C097018:P protein, Simian parainfluenza virus 5; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C097019:V protein, Simian parainfluenza virus 5; D014764:Viral Proteins; D015678:Viral Structural Proteins; D007372:Interferons