The analysis of genetic data for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type 1 (HTLV-1) is essential to improve treatment and public health strategies as well as toRecent advances have led to an unprecedented increase in sequence data for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type 1 (HTLV-1). For example, the number of HIV-1 sequences in GenBank had increased from approximately 42,000 in September 2000 (Gaschen et al. 2001) to nearly 115,000 sequences on September 2004. These sequences are also a valuable source of data for genetic analyses, such as the HIV-1 drug resistance study in which mutations into protease and reverse transcriptase genes can be used to better manage antiretroviral treatment (Shafer et al. 2000). Vaccine initiatives use sequences from the immunodominant regions of the viruses to design artificial peptides that stimulate the immune system and control the viral replication (Addo et al. 2001). Other research projects are evaluating whether the HTLV-1 envelope protein immunodominant region could elicit neutralizing antibody responses against HTLV-1. Such information could be used in the development of vaccines and to improve diagnostic methods (Sundaram et al. 2004).The post-translational modifications in the virus proteins are essential for HIV-1 and HTLV-1 fitness, assembly, and immune escape. The most frequent modifications are N-glycosilation, N-myristylation, and phosphorylation by protein kinases (Adachi et al. 1992, Reitter et al. 1998, Ono et al. 2000, Bouamir et al. 2003, Grassmann et al. 2005 The HIV-1 epidemic in Brazil was initially dominated by HIV-1 subtype B ) and the virus spread to all the states in the country through different transmission routes. HIV-1 subtype F1 was first identified in Salvador and recombinants of subtypes B and F1 were identified in Rio de Janeiro . A more recent heterosexual epidemic, characterized by the presence of subtype C viruses, was identified in South Brazil , Soares et al. 2003. Other reports have also demonstrated that distinct HIV-1 subtypes (A, B, C, D, F1) and recombinant forms (B/C, B/ F1) are actively participating in the Brazilian Aids epidemic (Morgado et al. 1998, Caride et al. 2001, Soares et al. 2005, Couto-Fernandez et al. 2005, Barreto et al. 2006, De Sa Filho et al. 2006).Financial support: Fapesp, PN-DST/AIDS +Corresponding author: lalcan@cpqgm.fiocruz.br ATLQ and ACAM-M contribute equally to this paper.
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, physicochemical 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.Key words: human T-cell lymphotropic virus type 1 -Env -Pol -epitopeThe human t-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia lymphoma (ATLL) (Poiesz et al. 1980) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) (Gessain et al. 1985, Osame et al. 1986). This infection is endemic in Japan, in the Caribbean Basin, some South American, and African regions (Mueller 1991), while there are 2.5 million HTLV-1 infected people in Brazil (Carneiro-Proietti et al. 2002). In contrast, only 5% of infected people develop the associated disease, and it is not yet known why 95-98% of them remain asymptomatic. The envelope glycoproteins of this virus are known to play a critical role in the infection process. The surface glycoprotein (gp46) subunit is involved in cellular receptor recognition, while the transmembrane glycoprotein (gp21) subunit anchors the gp46 to the cell and plays a major role in the post-binding steps of the fusion process, resulting in the formation of multinucleated giant cells named syncytia. These envelope proteins are expressed on the surface of virus-infected cells and on viral particles and they are the first to be recognized by the host in the course of the natural immune response (Nagy et al. 1983, Palker et al. 1989), in such a way that HTLV-1 infected individuals develop a strong immune response to the envelope (env) gene products. Several studies have focused on mapping linear immunodominant regions of the HTLV-1 surface glycoprotein that could elicit antibody responses, for the purpose of vaccine development and diagnostic screening (Tana...
Genetic analysis of HIV-1 is essential to improve treatment strategies and select epitopes for vaccine programs. The objective of this study was to determine whether known CD4 + and CD8 + epitopes were present in Brazilian HIV-1 strains. We used previously described CD8 + and CD4 + epitopes from the Los Alamos laboratory to search for these epitopes in the Brazilian sequences using the HIVbase program and we compared the frequency results with the analyses using physical-chemical profile tools from Network Protein Sequence Analysis (NPSA), and the SYFPEITHI program. Furthermore, this analysis was carried out with the Prosite tool using the GeneDoc program and ds/dn analyses using the Synonymous Nonsynonymous Analysis Program (SNAP). The HIVbase epitope mapping demonstrated that 30 CD8 + and 6 CD4 + epitopes were present in the Brazilian sequences at a high frequency. Only two of these epitopes were heavily glycosylated. Interestingly, ds/dn analyses showed evidence of purifying selective pressure. These types of analyses could be useful for the assessment of possible vaccine efficiency in populations.
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
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