Activities Reports
Transcrição
Activities Reports
ANNUAL ACTIVITY REPORT 2009 – 2010 National Institute of Science and Technology in Dengue Coordinator: Mauro Martins Teixeira Vice-Coordinator: Luiz Tadeu Moraes Figueiredo Mananger of Project: Fernanda de Araújo Rocha Host Institution: Department of Biochemistry and Immunology – Institute of Biological Sciences – UFMG Av. Antônio Carlos, 6627, Pampulha Belo Horizonte, MG, 30270-901 Tel.: (31) 3409-2502, FAX: (31) 3409-2651 Contact: [email protected] / [email protected] / [email protected] Webpage: http://www.icb.ufmg.br/inctemdengue 1 IDENTIFICATION OF THE TEAM The "National Institute of Science and Technology in Dengue" is hosted by the Institute of Biological Sciences at Universidade Federal de Minas Gerais (UFMG) and formed by other 10 Research Institutions, Universities and Companies belonging to 6 different states in Brazil. The team of the Institute consists of 29 researchers. The following tables shows the name and institution of each member of the research team: Managing core Name Institution Álvaro Eiras UFMG Ana Cristina Lima Leite UFPE Luís Tadeu Moraes Figueiredo – Vice-Coordinator FMRP-USP Marcelo Bozza UFRJ Mauro Martins Teixeira - Coordinator UFMG Senior Researchers Name # Adla Betsaida Martins Teixeira 01 Alaíde Braga de Oliveira 02 Álvaro Eiras 03 Alzira Batista Cecílio 04 Ana Cristina Lima Leite 05 Andréa Da Poian 06 Antônio Helvécio Totola 07 Antônio Lúcio Teixeira Jr 08 Arlene de Jesus Mendes Caldas 09 Cláudia N. Paiva 10 Cláudio Bonjardim 11 Daniela M. A. Ferraz Navarro 12 Danielle da Glória de Souza 13 Divaldo de Almeida Sampaio 14 Edson Holanda Teixeira 15 Erna Kroon 16 Fernando Antônio Botoni 17 Fernão Castro Braga 18 Jaqueline Germano de Oliveira 19 Lirlândia Sousa 20 Luciana Barros de Arruda Hinds 21 Luís Tadeu Moraes Figueiredo 22 Marcelo Bozza 23 Mauro Martins Teixeira 24 Rachel Oliveira Castilho 25 Rose Lisieux R. P. Jacome 26 Sérgio Oliveira De Paula 27 Silvania Nascimento 28 Vanessa Pinho da Silva 29 Victor Hugo Aquino Quintana 30 Institution UFMG UFMG UFMG FUNED UFPE UFRJ UFSJ UFMG UFMA UFRJ UFMG UFPE/HEMOPE UFMG UFPE/HEMOPE UFCE UFMG UFMG UFMG CPqRR/Fiocruz UFMG UFRJ FMRP-USP UFRJ UFMG UFMG UFMG UFV UFMG UFMG FMRP-USP 2 FULL NAME OF THE ASSOCIATED INSTITUTIONS MINAS GERAIS • ICB-UFMG: Institute of Biological Sciences/Universidade Federal de Minas Gerais/MG; • UFSJ: Universidade Federal de São João Del Rey; • UFV: Universidade Federal de Viçosa; • CPqRR/Fiocruz: Centro de Pesquisas René Rachou / Fiocruz; • FUNED: Fundação Ezequiel Dias RIO DE JANEIRO • UFRJ: Universidade Federal do Rio de Janeiro; SÃO PAULO • FMRP-USP: Faculdade de Medicina de Ribeirão Preto – Universidade de São Paulo; PERNAMBUCO • UFPE: Universidade Federal de Pernambuco • HEMOPE: Fundação de Hematologia e Hemoterapia de Pernambuco - PE MARANHÃO • UFMA: Universidade Federal do Maranhão CEARÁ • UFCE: Universidade Federal do Ceará MAIN RESEARCH TOPICS The main themes at which the National Institute of Science and Technology in Dengue place its focus are: (A) the development of animal models of disease and pathophysiology of dengue virus infection, (B) identification of the interaction between dengue virus and human cells, (C) to study the clinical presentation of disease, develop biomarkers and prepare the infra-structure to perform clinical trials in patients with dengue; (D) evaluate the molecular epidemiology of dengue infection in Brazil; (E) develop and nationalize diagnostic tests adapted to the Brazilian situation; 3 (F) Screen the Brazilian flora in search of natural products and synthetic compounds against the virus; (G) develop new strategies to control and eliminate the vector; (H) develop appropriate education and communication programs to instruct the public of dengue in an attempt to change attitudes towards the disease and vector. A. Animal models of disease and the pathophysiology of Dengue infection Group leaders: Mauro Teixeira, Danielle Souza Senior group members: Vanessa Pinho, Lirlândia Sousa, Erna Kroon, Marcelo Bozza, Luciana Arruda-Hinds, Antonio Lucio Teixeira Jr, Ana Cristina Leite. B. The interaction between Dengue virus and human cells Group leaders: Marcelo Bozza, Andrea da Poian Senior group members: Luciana Arruda-Hinds, Lirlândia Sousa, Mauro Teixeira, Claudio Bonjardim, Cláudia Paiva, Tatiana Porto. C. Clinical presentation of disease, biomarkers and clinical trials Group leaders: Arlene Caldas, Antonio L Teixeira Senior group members: Mauro Teixeira, Fernando Antonio Botoni, Ana Cristina Leite, Marcelo Bozza, Divaldo de Almeida Sampaio, Edson Teixeira. D. The molecular epidemiology of Dengue infection in Brazil Group leaders: Luiz Tadeu Figueiredo, Erna Kroon Senior group members: Victor Quintana, Jaquelline Oliveira, Alzira Cecílio, Luiz Leomil Coelho, Gustavo Ferreira, Mauro Teixeira. E. Diagnostic tests adapted to the Brazilian situation Group leaders: Luiz Tadeu Figueiredo, Victor Quintana Senior group members: Antonio Totola, Mauro Teixeira, Erna Kroon F. Screening the Brazilian flora for natural products and synthetic compounds active against the virus Group leaders: Alaíde Braga, Ana Cristina Leite Senior group members: Fernão Braga, Rose Jácome, Erna Kroon, Mauro Teixeira, Daniela Navarro 4 G. Vector biology and control using advanced methodologies Group leaders: Alvaro Eiras Senior group members: Erna Kroon, Ana Cristina Leite, Daniela Navarro H. Education and Communication in Dengue Leader Group: Adla Teixeira Senior group members: Silvania Nascimento SUMMARY OF RESULTS AND PERSPECTIVES In this first year of activities 61 scientific papers have been published and there were 09 Ph.D. theses and 12 dissertations on the topic of dengue being developed. The major advances achieved so far reflect the current strength of the group in studying the pathophysiology of dengue disease, our capacity to perform molecular epidemiology studies and our efforts to develop new diagnostic tools for the disease. We will highlight below the major achievements. - We have identified platelet-activating factor receptor (PAFR) as a major disease associated gene in the context of dengue and have confirmed this in two different experimental models of the disease. A patent application was filed, the PAFR was synthesized in clinical grade and a clinical trial with PAFR antagonists is planned for the next year. - We have prepared the center in Belo Horizonte for human studies and have confirmed the usefulness of NS1 measurement for detection of infection in suspected cases. - Further experiments in vitro and in vivo have suggested the possibility that other mediators of inflammation may be useful targets for the treatment of severe dengue, including the cytokine MIF and bradykinin and chemokine receptors. - In vitro studies on the mechanism of E protein mediated fusion of dengue virus have unraveled a fundamental role of the residue 101, suggesting it may be used as pharmacological target to prevent viral entry into cells. - Diagnostic tests based on PCR and ELISA tests have been developed and tested in the laboratory. The possibility of transferring these tests into the clinic and commercializing is being evaluated with industrial partners. 5 - We have been developing the necessary techniques and methods to screen for anti-viral activity and have established collaborations with academic and industrial partners to facilitate screening and access to new compounds. - There have been exciting new developments with mosquito traps and we are setting up the necessary strategy to evaluate whether traps are useful to control mosquito populations, in addition to being helpful for epidemiological vigilance. - Finally, we are actively studying materials which are produced to inform the population of dengue. These materials will form the bases to suggest novel education and communicational strategies that, we hope, will impact on the way the population deals with the epidemy. SELECTED LIST OF PUBLICATIONS • Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection. Souza DG, Fagundes CT, Sousa LP, Amaral FA, Souza RS, Souza AL, Kroon EG, Sachs D, Cunha FQ, Bukin E, Atrasheuskaya A, Ignatyev G, Teixeira MM. Proc Natl Acad Sci USA 2009; 106(33): 14138-43. • Contribution of macrophage migration inhibitory factor to the pathogenesis of dengue virus infection. Assunção-Miranda I, Amaral FA, Bozza FA, Fagundes CT, Sousa LP, Souza DG, Pacheco P, Barbosa-Lima G, Gomes RN, Bozza PT, Da Poian AT, Teixeira MM, Bozza MT. FASEB J. 2010; 24(1):218-28. • Dengue virus capsid protein usurps lipid droplets for viral particle formation. Samsa MM, Mondotte JA, Iglesias NG, Assunção-Miranda I, Barbosa-Lima G, Da Poian AT, Bozza PT, Gamarnik AV. PLoS Pathog. 2009; 5(10):e1000632. • Interaction of the Dengue virus fusion peptide with membranes assessed by NMR: The essential role of the envelope protein Trp101 for membrane fusion. Melo MN, Sousa FJ, Carneiro FA, Castanho MA, Valente AP, Almeida FC, Da Poian AT, Mohana-Borges R. J Mol Biol. 2009; 392(3):736-46. • Dengue virus 3 genotype I in Aedes aegypti mosquitoes and eggs, Brazil, 20052006. Vilela AP, Figueiredo LB, dos Santos JR, Eiras AE, Bonjardim CA, Ferreira PC, Kroon EG. Emerg Infect Dis. 2010; 16(6):989-92 • Detection of dengue virus in saliva and urine by real time RT-PCR. Poloni TR, Oliveira AS, Alfonso HL, Galvão LR, Amarilla AA, Poloni DF, Figueiredo LT, Aquino VH. Virol J. 2010; 7:22 6 • Almeida, S. J., Ricardo Poley Martins Ferreira, Eiras, A. E, Obermayr, R. P., Geier, Martin. Multi-agent Modeling and Simulation of a Mosquito Population of the mosquito Aedes aegypti.. Environmental Modelling & Software. , v.26, p.1 - 18, 2010. • Eiras, A.E, Resende, Marcelo Carvalho. Preliminary evaluation of the "DengueMI" technology for Aedes aegypti monitoring and control. Cadernos de Saúde Pública (ENSP. Impresso). , v.25, p.45 - 58, 2009 • New genotype of dengue type 3 virus circulating in Brazil and Colombia showed a close relationship to old Asian viruses. Aquino VH, Amarilla AA, Alfonso HL, Batista WC, Figueiredo LT. PLoS One. 2009;4(10):e7299. • Genetic diversity of the E protein of dengue type 3 virus. Amarilla AA, de Almeida FT, Jorge DM, Alfonso HL, de Castro-Jorge LA, Nogueira NA, Figueiredo LT, Aquino VH. Virol J. 2009;6:113. • Mosquitoes infected with dengue viruses in Brazil. de Figueiredo ML, de C Gomes A, Amarilla AA, de S Leandro A, de S Orrico A, de Araujo RF, do Sm Castro J, Durigon EL, Aquino VH, Figueiredo LT. Virol J. 2010;7:152. • Antimicrobial, antiviral and cytotoxic activity of extracts and constituents from Polygonum spectabile Mart. Brandão GC, Kroon EG, Duarte MG, Braga FC, de Souza Filho JD, de Oliveira AB. Phytomedicine. 2010; in press. • Dengue virus 3 clinical isolates show different patterns of virulence in experimental mice infection. Ferreira GP, Figueiredo LB, Coelho LF, S PA Jr, Cecilio AB, Ferreira PC, Bonjardim CA, Arantes RM, Campos MA, Kroon EG. Microbes Infect. 2010;12(7):546-54. 7