Apical membrane antigen 1 (AMA1): analysis of genetic diversity in isolates of Plasmodium vivax from the Brazilian Amazon

• Grant number: 13/08267-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2013
• Effective date (End): June 30, 2015
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Letusa Albrecht
• Grantee: Natália Silveira Virgili
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Each year, the malaria parasite, Plasmodium vivax infects 70 to 80 million people worldwide. In Brazil, P. vivax is responsible for 83.6% of malaria cases, being considered as the most frequent species of plasmodium in the country. Unlike Plasmodium falciparum, infections caused by P. vivax are rarely lethal. However, P. vivax has a significant impact on the productivity of local populations as the course of infection is usually prolonged and the development of acquired immunity in endemic areas takes several years. The recent emergence of drug-resistant strains further complicates infection by P. vivax which leads to the intensified research on alternative control methods, such as the development of vaccines. AMA-1 is a protein that is involved in invasion of parasites of the phylum Apicomplexa in host cells, participating in the formation of joint motion. This protein contains four regions, these being, pro-sequence, a cysteine rich ectodomain, transmembrane domain and a cytoplasmic region. In the ectodomain, the disulfide bridges formed by cysteine residues, allow their separation into three domains, designated I, II and III. The biological importance of this protein can be detached, because attempts to silence the AMA-1 gene of P. falciparum and Toxoplasma gondii generated unviable parasites, showing that this protein is essential for parasite survival. The highest rate of mutations and genetic diversity has been shown in domain I, however, the domain II has a high degree of conservation of amino acid sequences and is the most immunogenic region in Plasmodium falciparum as much as in Plasmodium vivax. As this genetic diversity can jeopardize the effectiveness of a vaccine containing this antigen, the main objective of this work is to characterize the pattern of diversity of protein AMA-1 of P. vivax isolates from the Brazilian Amazon. (AU)