Mapping the molecular characteristics of Brazilian human T-cell lymphotropic virus type 1 Env (gp46) and Pol amino acid sequences for vaccine design.
This study was carried out to evaluate the molecular pattern of all available Brazilian human T-cell lymphotropic virus type 1 Env (n = 15) and Pol (n = 43) nucleotide sequences via epitope prediction, physico-chemical analysis, and protein potential sites identification, giving support to the Brazilian AIDS vaccine program. In 12 previously described peptides of the Env sequences we found 12 epitopes, while in 4 peptides of the Pol sequences we found 4 epitopes. The total variation on the amino acid composition was 9 and 17% for human leukocyte antigen (HLA) class I and class II Env epitopes, respectively. After analyzing the Pol sequences, results revealed a total amino acid variation of 0.75% for HLA-I and HLA-II epitopes. In 5 of the 12 Env epitopes the physico-chemical analysis demonstrated that the mutations magnified the antigenicity profile. The potential protein domain analysis of Env sequences showed the loss of a CK-2 phosphorylation site caused by D197N mutation in one epitope, and a N-glycosylation site caused by S246Y and V247I mutations in another epitope. Besides, the analysis of selection pressure have found 8 positive selected sites (w = 9.59) using the codon-based substitution models and maximum-likelihood methods. These studies underscore the importance of this Env region for the virus fitness, for the host immune response and, therefore, for the development of vaccine candidates.
Mota-Miranda
Aline Cristina
AC
Laboratório Avançado de Saúde Pública, Centro de Pesquisa Gonçalo Moniz, Fiocruz, Salvador, BA, 40296-610, Brasil. lalcan@cpqgm.fiocruz.br
de-Oliveira
Tulio
T
Moreau
Domingos Ramon
DR
Bomfim
Catarina
C
Galvão-Castro
Bernardo
B
Alcantara
Luiz Carlos
LC
D000595:Amino Acid Sequence; D001483:Base Sequence; D015195:Drug Design; D018604:Epitope Mapping; D015686:Gene Products, env / Q000235:genetics* / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines
D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D014765:Viral Vaccines; C055266:gp46 protein, Human T-cell leukemia virus type I