B-cell epitopes of the envelope glycoprotein of caprine arthritis-encephalitis virus and antibody response in infected goats.
Goats infected with caprine arthritis-encephalitis virus (CAEV) develop high titres of antibodies to Env. Not only is no consistent neutralizing response found but anti-Env antibodies have even been associated with disease in infected goats. To identify the continuous antigenic determinants involved in this atypical anti-Env response, we mapped CAEV-CO Env by screening an epitope expression library with infected goat sera. In addition to the four previously described epitopes, seven novel antigenic sites were identified, of which five were located on the surface (SU) and two in the transmembrane (TM) subunits of Env. The SU antibody-binding domains located in the variable regions of the C-terminal part of the molecule (SU3 to SU5) showed the strongest reactivity and induced a rapid seroconversion in six experimentally infected goats. However, the response to these immunodominant epitopes did not appear to be associated with any neutralizing activity. The pattern of serum reactivity of naturally infected goats with these epitopes was restricted, suggesting a type-specific reaction. Interestingly, the reactivity of peptides representing SU5 sequences derived from CAEV field isolates varied with the geographical and/or breeding origin of the animals. This suggests that peptides corresponding to the immunodominant SU epitopes may well be useful in the serotyping of CAEV isolates. Furthermore, the identification of the CAEV Env epitopes will permit us to functionally dissect the antibody response and to address the role of anti-Env antibodies either in the protection from or in the pathogenesis of CAEV infection.
Bertoni
Giuseppe
G
Institute of Veterinary Virology, University of Berne, Länggass-Str. 122, CH-3012 Berne, Switzerland1.
Hertig
Christian
C
Institute of Veterinary Virology, University of Berne, Länggass-Str. 122, CH-3012 Berne, Switzerland1.
Zahno
Marie-Luise
ML
Institute of Veterinary Virology, University of Berne, Länggass-Str. 122, CH-3012 Berne, Switzerland1.
Vogt
Hans-Rudolf
HR
Institute of Veterinary Virology, University of Berne, Länggass-Str. 122, CH-3012 Berne, Switzerland1.
Dufour
Sophie
S
Institute of Veterinary Virology, University of Berne, Länggass-Str. 122, CH-3012 Berne, Switzerland1.
Cordano
Pablo
P
Institute of Veterinary Virology, University of Berne, Länggass-Str. 122, CH-3012 Berne, Switzerland1.
Peterhans
Ernst
E
Institute of Veterinary Virology, University of Berne, Länggass-Str. 122, CH-3012 Berne, Switzerland1.
Cheevers
William P
WP
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164-7040, USA2.
Sonigo
Pierre
P
Génétique des Virus (ICGM-CNRS UPR 0415), Institut Cochin de Génétique moléculaire, 75014 Paris, France3.
Pancino
Gianfranco
G
Génétique des Virus (ICGM-CNRS UPR 0415), Institut Cochin de Génétique moléculaire, 75014 Paris, France3.
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016088:Arthritis-Encephalitis Virus, Caprine / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D001665:Binding Sites; D015153:Blotting, Western; D003001:Cloning, Molecular; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins; D006041:Goats / Q000276:immunology* / Q000821:virology*; D007106:Immune Sera / Q000096:biosynthesis / Q000276:immunology; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016180:Lentivirus Infections / Q000276:immunology* / Q000662:veterinary; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D019151:Peptide Library; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D013997:Time Factors; D014764:Viral Proteins
D000914:Antibodies, Viral; D000956:Antigens, Viral; C412317:ENV protein, Caprine arthritis encephalitis virus; D018985:Epitopes, B-Lymphocyte; D015686:Gene Products, env; D006023:Glycoproteins; D007106:Immune Sera; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; D019151:Peptide Library; D011994:Recombinant Proteins; D014764:Viral Proteins