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
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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
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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;
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(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
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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.
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- 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
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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
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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.
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