title: Mutational analysis of a principal neutralization domain of visna/maedi virus envelope glycoprotein.
abstract: We have shown previously that a type-specific neutralization domain is located within a 39 aa sequence in the fourth variable domain of gp135 in visna/maedi virus. We now show that neutralizing antibodies detected early in infection are directed to this epitope, suggesting an immunodominant nature of this domain. Ten antigenic variants were previously analysed for mutations in this region, and all but one were found to be mutated. To assess the importance of these mutations in replication and neutralization, we reconstructed several of the mutations in an infectious molecular clone and tested the resulting viruses for neutralization phenotype and replication. Mutation of a conserved cysteine was shown to alter the neutralization epitope, whilst the replication kinetics in macrophages were unchanged. Mutations modulating potential glycosylation sites were found in seven of the ten antigenic variants. A frequently occurring mutation, removing a potential glycosylation site, had no effect on its own on the neutralization phenotype of the virus. However, adding an extra potential glycosylation site in the region resulted in antigenic escape. The results indicate that the conserved cysteine plays a role in the structure of the epitope and that glycosylation may shield the principal neutralization site.
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Benedikta S
authors.initials: BS
authors.lastname: Haflidadóttir
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Sigrídur
authors.initials: S
authors.lastname: Matthíasdóttir
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Gudrún
authors.initials: G
authors.lastname: Agnarsdóttir
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Sigurbjorg
authors.initials: S
authors.lastname: Torsteinsdóttir
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Pétursson
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Ólafur S
authors.initials: ÓS
authors.lastname: Andrésson
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Andrésdóttir
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology / Q000821:virology; D003545:Cysteine / Q000737:chemistry*; D006031:Glycosylation; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011021:Pneumonia, Progressive Interstitial, of Sheep / Q000276:immunology / Q000821:virology; D012756:Sheep; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D014790:Visna-maedi virus / Q000235:genetics* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins; C089034:glycoprotein 135, Maedi visna virus; D003545:Cysteine