Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions

Abstract

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.

Selective deficit in antibodies specific for the superantigen binding site of gp120 in HIV infection

“…Inasmuch as the RPs and SPs we have examined had approximately 19 mg/ml of total serum IgG, about 0.4 to 1.5 mg/ml of their IgG's are gp120 specific. Assuming that gp120 encompasses no more than 10 epitopes (31,32), we estimate that the serum samples we tested contained 40 to 150 mg/ml of epitope-specific IgG antibodies and that, at 1/50 serum dilutions, 0.8 to 3 mg/ml of epitope-specific antibody were tested. Thus, with a sensitivity limit of 50 ng/ml, the ELISA test we used could not have missed the presence of C4-and V4-specific V H 3 / antibodies.…”

Relationship of HIV‐1 Envelope V2 and V3 Sequences of the Primary Isolates to the Viral Phenotype

“…Genetic variability within the human immunodeficiency virus type 1 (HIV-1) genome is most pronounced in the env gene, in which nucleotide substitutions, duplications, and deletions produce extensive amino acid diversity within five hypervariable domains in the envelope glycoprotein. The hypervariable domains, designated V1 through V5, are interspersed with conserved regions along the gp120 molecule (20,22,33). Sequence variation in the env gene can affect the biological phenotype with respect to the replication rate in different cells, as well as cytotropism and the capacity to induce syncytia in vitro (4,5,8,13,15,23,24,26,35).…”

A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41

“…Analysis of the primary amino acid sequence of gp41 reveals several segments that are hydrophobic or highly amphiphilic (Muesing et al. 1985;Modrow et al, 1987;Eisenberg & Wesson, 1990). Such segments have been proposed to play major roles in mediating membrane interactions (Kaiser & Kezdy, 1984;Lucy, 1984;Hoekstra, 1990).…”