title: Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication.
abstract: The genetic variation of equine infectious anaemia virus (EIAV) clearly affects the antigenic properties of the viral envelope; however, effects on immunogenicity remain undefined, although widely assumed. Here, the immunogenicity is reported of a novel, neutralization-resistant, pony-isolate envelope EIAV(PV564DeltaPND) that contains a 14-residue deletion in the designated principal neutralizing domain (PND) of the gp90 protein. Two ponies inoculated with a chimeric virus, EIAV(DeltaPND), containing the EIAV(PV564DeltaPND) envelope in a reference provirus strain, remained asymptomatic through 14 months post-inoculation, producing high steady-state levels of envelope-specific antibodies but no detectable serum-neutralizing antibodies. Consequent dexamethasone-induced immune suppression produced characteristic EIA that resolved concomitantly with the development of high-titre, strain-specific, neutralizing antibodies and a 100-fold reduction in steady-state virus loads. These results demonstrate: natural variations in the EIAV envelope have profound effects on both antigenic and immunogenic properties; the PND is not required for neutralizing antibody responses; and transient immune suppression can enhance established host immunity to achieve more effective control of steady-state lentivirus replication.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Craigo
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
authors.forename: Caroline
authors.initials: C
authors.lastname: Leroux
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
authors.forename: Laryssa
authors.initials: L
authors.lastname: Howe
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Steckbeck
authors.affiliation: Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA2.
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Cook
authors.affiliation: Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA2.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Issel
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D002353:Carrier State / Q000276:immunology / Q000662:veterinary*; D003907:Dexamethasone / Q000494:pharmacology; D004859:Equine Infectious Anemia / Q000276:immunology* / Q000821:virology; D017353:Gene Deletion; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006736:Horses; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology; D004860:Infectious Anemia Virus, Equine / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D011995:Recombination, Genetic; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D012367:RNA, Viral; C091940:SU protein, equine infectious anemia virus; D014759:Viral Envelope Proteins; D003907:Dexamethasone