Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions.
Independent isolates of human immunodeficiency virus (HIV) exhibit a striking genomic diversity, most of which is located in the viral envelope gene. Since this property of the HIV group of viruses may play an important role in the pathobiology of the virus, we analyzed the predicted amino acid sequences of the envelope proteins of seven different HIV strains, three of which represent sequential isolates from a single patient. By using a computer program that predicts the secondary protein structure and superimposes values for hydrophilicity, surface probability, and flexibility, we identified several potential antigenic epitopes in the envelope proteins of the seven different viruses. Interestingly, the majority of the predicted epitopes in the exterior envelope protein (gp120) were found in regions of high sequence variability which are interspersed with highly conserved regions among the independent viral isolates. A comparison of the sequential viral isolates revealed that changes concerning the secondary structure of the protein occurred only in regions which were predicted to be antigenic, predominantly in highly variable regions. The membrane-associated protein gp41 contains no highly variable regions; about 80% of the amino acids were found to be conserved, and only one hydrophilic area was identified as likely to be accessible to antibody recognition. These findings give insight into the secondary and possible tertiary structure of variant HIV envelope proteins and should facilitate experimental approaches directed toward the identification and fine mapping of HIV envelope proteins.
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000595:Amino Acid Sequence; D000939:Epitopes / Q000032:analysis*; D006678:HIV / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D012984:Software; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
D000939:Epitopes; D014759:Viral Envelope Proteins