Levels of HIV1 gp120 3D B-cell epitopes mutability and variability: searching for possible vaccine epitopes.
We used a DiscoTope 1.2 (http://www.cbs.dtu.dk/services/DiscoTope/), Epitopia (http://epitopia.tau.ac.il/) and EPCES (http://www.t38.physik.tu-muenchen.de/programs.htm) algorithms to map discontinuous B-cell epitopes in HIV1 gp120. The most mutable nucleotides in HIV genes are guanine (because of G to A hypermutagenesis) and cytosine (because of C to U and C to A mutations). The higher is the level of guanine and cytosine usage in third (neutral) codon positions and the lower is their level in first and second codon positions of the coding region, the more stable should be an epitope encoded by this region. We compared guanine and cytosine usage in regions coding for five predicted 3D B-cell epitopes of gp120. To make this comparison we used GenBank resource: 385 sequences of env gene obtained from ten HIV1-infected individuals were studied (http://www.barkovsky.hotmail.ru/Data/Seqgp120.htm). The most protected from nonsynonymous nucleotide mutations of guanine and cytosine 3D B-cell epitope is situated in the first conserved region of gp120 (it is mapped from 66th to 86th amino acid residue). We applied a test of variability to confirm this finding. Indeed, the less mutable predicted B-cell epitope is the less variable one. MEGA4 (standard PAM matrix) was used for the alignments and "VVK Consensus" algorithm (http://www.barkovsky.hotmail.ru) was used for the calculations.
Khrustalev
Vladislav Victorovich
VV
Department of General Chemistry, Belarussian State Medical University, Minsk 220000, Belarus. vvkhrustalev@mail.ru
D000595:Amino Acid Sequence; D000940:Antigenic Variation / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis*; D030561:Databases, Nucleic Acid; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D014765:Viral Vaccines
D004279:DNA, Viral; D018985:Epitopes, B-Lymphocyte; D015699:HIV Envelope Protein gp120; D014765:Viral Vaccines; C514793:gp120 protein, Human immunodeficiency virus 1