AnÃlise in silico da HSP83 de Leishmania chagasi: implicaÃÃes para antigenicidade e evoluÃÃo

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

Protozoan parasites belonging to the genus Leishmania are transmitted between mammalian hosts by bloodsucking sand flies and are the etiological agents of the four clinical forms of leishmaniasis: the fatal visceral form, mucocutaneous leishmanasis, cutaneous leishmaniasis and the rare diffuse cutaneous leishmaniasis. Visceral leishmaniases is common in less developed countries, with an estimated 500.000 new cases each year. Leishmania chagasi is the etiological agent of visceral leishmaniases in the Americas and other Leishmania species are responsible for the visceral form of the disease in the Old World. Because of their importance, the development of drugs and vaccines using parasite antigens have been the subject of many studies. Among major parasite antigen are the heat shock proteins (HSP), a major classes of conserved protein, classified as molecular chaperones. They are essential in cell cycle control, involved in assisting cellular protein folding and preventing irreversible side-reactions such as unspecific aggregation. The HSP may play a role as immunoregulatory agents with potent therapeutic use; furthermore, they have been identified as major immunogens in several infectious diseases and usually elicit specific protective responses. HSP83 of Leishmania chagasi, the parasite ortholog to HSP90, is one of the most abundant proteins and is strongly recognized by both humoral and cellular immune responses in human and canine visceral leishmaniasis. In the present study, based on the alignment of coding regions from HSP genes of different origins, the primary structure of the HSP83 was compared to HSP90 from others organisms order to infer phylogenetic relationships. When the deduced amino acid sequence was compared to sequences deposited at public gene banks, it was evident that the protein is highly conserved among organism belonging to different kingdoms. When the coding sequence was compared, it was possible to rigorously map the exons from the human gene over the whole extension of the parasite HSP83 ortholog, except for three gaps in the parasite sequence. The first gap corresponds to the flexible hinge between beta sheets in the N-terminal domain, the second has 57aa (largest gap) and corresponds to the hinge between the N-terminal and the middle domains and the last gap corresponds also to a flexible hinge between the middle and the carboxy domains. Portions with increased divergence along sequence are coincident with the equivalent exon junctions in the orthologous mammalian gene. We show that the antigenic epitopes are preferentially distributed over non-functional, divergent areas. Our results also suggest that the HSP83 gene from trypanosomatid ancestors had introns that were lost during evolution

ASSUNTO(S)

antigenicidade leishmania chagasi hsp83 hsp83 antigenicity leishmania chagasi genetica visceral leishmaniasis phylogenetic analysis anÃlise filogenÃtica leishmaniose visceral

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