Dados do Trabalho

Título

EVALUATION OF GENETIC POLYMORPHISM OF Plasmodium falciparum MEROZOITE SURFACE PROTEINS DUFFY BINDING-LIKE (MSPDBL) -1 AND MSPDBL-2 AND ITS IMPACT ON B AND T IMMUNODOMINANT EPITOPES IN BRAZILIAN MALARIA ENDEMIC AREAS

Introdução

Merozoite Surface Protein Duffy Binding-like -1 and -2 (MSPDBL-1 and MSPDBL-2) are proteins that bind directly to MSP-1 on the surface of the parasite, forming a complex on the erythrocyte surface through its DBL domain facilitating the invasion of P. falciparum into the erythrocyte. Considering that the extensive genetic diversity exhibited by P. falciparum is an important factor for the parasite's evasion of the host immune system, we believe that the presence of polymorphisms in the genetic regions encoding the MSPDBL-1 and -2 proteins may modulate specific immune response.

Objetivo (s)

Here, we propose to identify genetic polymorphisms and to evaluate the impact of these polymorphisms on the potentially antigenic regions in the Duffy Binding-like (DBL) and Secreted Polymorphic Antigen Associated With Merozoite (SPAM) domains of the MSPDBL-1 and MSPDBL-2 proteins in P. falciparum isolates circulating in Brazilian-malaria endemic areas.

Material e Métodos

Sixty-five isolates from Cruzeiro do Sul and Mâncio Lima (Acre State) and Guajará (Amazonas State), Brazilian Amazon, were collected. Genomic DNA was extracted, the gene region encoding DBL and SPAM domains was sequenced and the impact of polymorphisms on the potentially antigenic regions was evaluated. Intrapopulation genetic diversity and Tajima’s D test values were calculated using specific software’s. B-cell and T-cell epitopes were identify using BCPreds and IEBD, respectively.

Resultados e Conclusão

Twelve and forty polymorphisms were identified in the SPAM and DBL domains of MSPDBL-1, respectively. The MSPDBL-2 protein was more conserved, with three and one polymorphism in the respective SPAM and DBL domain. In the genetic analysis of the population, the DBL domains presented positive values for the TDT, while the SPAM domains were negative, however we did not observe statistically significant values. The nucleotide diversity was higher in MSPDBL-1 than in MSPDBL-2. In silico prediction analysis of immunodominant B and T epitopes, considering the 3D7 reference sequence, showed fifteen B-cell epitopes and fifteen T-cell epitopes that are recognized with a frequency of 50% to 82% of MHC antigens. Our data suggest that P. falciparum isolates that circulate in Brazilian Amazon present an extensive genetic diversity and the gene region that encodes MSPDBL-1 presents a greater genetic diversity when compared to MSPDBL-2, mainly in the gene region encoding DBL domain.

Palavras-chave

Malaria, P. falciparum, Genetic polymorphism, MSPDBL-1 and -2.

Agradecimentos

FIOCRUZ, CAPES and FAPERJ.