Natural genetic diversity of the DBL domain of a novel member of the Plasmodium vivax erythrocyte binding-like proteins (EBP2) in the Amazon rainforest.

Fernandes, Gabriela M; Rodrigues-Mattos, Guilherme H; Torres, Letícia M; Guedes, Karla S; Fontes, Cor J F; Ntumngia, Francis B; Adams, John H; Brito, Cristiana F A; Kano, Flora S; de Sousa, Taís N; Carvalho, Luzia H

Fernandes, Gabriela M; Rodrigues-Mattos, Guilherme H; Torres, Letícia M; Guedes, Karla S; Fontes, Cor J F; Ntumngia, Francis B; Adams, John H; Brito, Cristiana F A; Kano, Flora S; de Sousa, Taís N; Carvalho, Luzia H.

Afiliación

Fernandes GM; Biologia Molecular e Imunologia da Malária, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil; Universidade Federal de Minas Gerais (UFMG), Departamento de Parasitologia, Belo Horizonte, Brazil.
Rodrigues-Mattos GH; Biologia Molecular e Imunologia da Malária, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
Torres LM; Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Guedes KS; Julio Muller School Hospital, Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, Mato Grosso, Brazil.
Fontes CJF; Julio Muller School Hospital, Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, Mato Grosso, Brazil.
Ntumngia FB; Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
Adams JH; Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
Brito CFA; Biologia Molecular e Imunologia da Malária, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
Kano FS; Biologia Molecular e Imunologia da Malária, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
de Sousa TN; Biologia Molecular e Imunologia da Malária, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden. Electronic address: tais.sousa@fiocruz.br.
Carvalho LH; Biologia Molecular e Imunologia da Malária, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil. Electronic address: luzia.carvalho@fiocruz.br.

Infect Genet Evol ; 123: 105628, 2024 Sep.

Article en En | MEDLINE | ID: mdl-38936525

ABSTRACT

ABSTRACT

In malaria parasites, the erythrocyte binding-like proteins (EBL) are a family of invasion proteins that are attractive vaccine targets. In the case of Plasmodium vivax, the widespread malaria parasite, blood-stage vaccines have been largely focused on a single EBL candidate, the Duffy binding-like domain (DBL) of the Duffy binding protein (DBPII), due to its well-characterized role in the reticulocyte invasion. A novel P. vivax EBL family member, the Erythrocyte binding protein (EBP2, also named EBP or DBP2), binds preferentially to reticulocytes and may mediate an alternative P. vivax invasion pathway. To gain insight into the natural genetic diversity of the DBL domain of EBP2 (region II; EBP2-II), we analyzed ebp2-II gene sequences of 71 P. vivax isolates collected in different endemic settings of the Brazilian Amazon rainforest, where P. vivax is the predominant malaria-associated species. Although most of the substitutions in the ebp2-II gene were non-synonymous and suggested positive selection, the results showed that the DBL domain of the EBP2 was much less polymorphic than that of DBPII. The predominant EBP2 haplotype in the Amazon region corresponded to the C127 reference sequence first described in Cambodia (25% C127-like haplotype). An overview of ebp2-II gene sequences available at GenBank (n = 352) from seven countries (Cambodia, Madagascar, Myanmar, PNG, South Korea, Thailand, Vietnam) confirmed the C127-like haplotype as highly prevalent worldwide. Two out of 43 haplotypes (5 to 20 inferred per country) showed a global frequency of 60%. The results presented here open new avenues of research pursuit while suggesting that a vaccine based on the DBL domain of EBP2 should target a few haplotypes for broad coverage.

Asunto(s)

Variación Genética; Malaria Vivax; Plasmodium vivax; Proteínas Protozoarias; Plasmodium vivax/genética; Proteínas Protozoarias/genética; Proteínas Protozoarias/metabolismo; Proteínas Protozoarias/química; Malaria Vivax/parasitología; Humanos; Bosque Lluvioso; Filogenia; Haplotipos; Antígenos de Protozoos/genética; Dominios Proteicos; Receptores de Superficie Celular

Palabras clave

Erythrocyte binding protein 2; Genetic polymorphism; Malaria; Plasmodium vivax; ebp2 gene

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium vivax / Variación Genética / Proteínas Protozoarias / Malaria Vivax Límite: Humans Idioma: En Revista: Infect Genet Evol Asunto de la revista: BIOLOGIA / DOENCAS TRANSMISSIVEIS / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos

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