Study on Brazilian arboviruses and rodent related viruses

• Grant number: 03/03682-3
• Support Opportunities: Research Projects - Thematic Grants
• Duration: February 01, 2004 - July 31, 2008
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Luiz Tadeu Moraes Figueiredo
• Grantee: Luiz Tadeu Moraes Figueiredo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Eurico de Arruda Neto

Abstract

This thematic research project includes 13 sub-projects on arboviruses and rodent related viruses that cause human diseases in Brazil. This project will be carried out in 4 years. The flavivirus dengue type 1 was introduced in Rio de Janeiro in 1986 and spread in Brazil causing large outbreaks. In 1991, dengue type 2 virus caused an outbreak in Rio de Janeiro where dengue hemorrhagic fever/dengue shock syndrome (dhf/dss) cases were first reported. Dengue became endemic in Brazil with circulation of 2 serotypes in cities infested by Aedes aegypti. After 1998, hundreds of thousands of dengue cases have been yearly reported in Brazil and the number dhf/dss cases were increased. In 2001, dengue type 3 virus was introduced into Rio de Janeiro. More than 800 000 dengue cases were reported in 2002 including more than a thousand of dhf/dss and about 100 fatalities cases. The situation of dengue in Brazil is worsening and it probably will become a serious public health problem as observed in the southeast of Asia. As part of this research project, molecular biology diagnostic methods of dengue, studies on dengue pathogenesis and genomic markers of dengue virus virulence will be studied. Sylvatic yeilow fever is expanding in Brazil related to a zoonosis of primates transmitted by haemagoggus mosquitoes. In the last 4 years, dozens of severe human cases of yellow fever, many of them lethal, were reported among people living close to the highly populated areas of Brasília, Goiânia and Belo Horizonte, as well as, in the north of the state of São Paulo. The urbanization of yellow fever threats Brazil, especially in cities infested by the Aedes aegypti vector. The attenuated 17dd yellow fever vaccine is highly immunogenic and it is a suitable tool in order to avoid urbanization of the disease. However, rare fatal cases occurred after vaccination and it could impair an intensive use of the vaccine. As part of this project, the structure and functional mechanism of the ns5 rna polymerase of yellow fever will be studied in order to allow further studies on antiviral specific drugs. The Orthobunyavirus oropouche is the causative agent of the second Brazilian arboviral disease in number of reported cases. The virus causes outbreaks of acute febrile illness and encephalitis in towns at the border of rivers of the Amazon region. Oropouche virus is maintained in urban cycles involving Culicoides paraensis vector and man. About 500 000 Brazilians were infected by Oropouche virus in the last decades. For this project, antiviral drugs will be tested against Oropouche virus, a hamster experimental model of Oropouche fever, virus propagation in cell cultures and mechanisms of virus replication will be studied, and a cold-adapted virus strain to be used as a vaccine will be created. The rodent related hantaviruses are cause of cardiopulmonary syndrome (hcps). The disease was firstly described in Brazil in 1993 and about 240 cases have been reported with a 40% fatality rare. We studied 14 of these cases presenting a prodromic fever that involved after 3 to 5 days to dyspnea, respiratory failure and shock. Thrombocytopenia and elevated hematocrit were also observed in these cases. We also developed a rt-pcr diagnostic method for hantavirus and detected virus genome in the blood of 11 hcps patients. Nucleotide sequences of rt -pcr amplicons from these patients showed a 96.5 to 87.7% homology with araraquara hantavirus genome, showing that these cases were caused by this virus. We also performed a serologic survey to hantavirus, in 2001, in Jardinópolis county, sp, including 818 participants, and 14.3% of them presented igg antibodies to andes hantavirus detected by ELISA. Soropositive participants were not associated to sex, age, previous contact with rodents or severe pneumonia. These results suggest that hantaviruses may be causing undiagnosed asymptomatic or clinically minor infections in Brazil. It entails important questions such as, whether more than one hantavirus would circulate in Jardinópolis, causing mostly benign infections. Would hcps be associated with some predisposing condition in the infected individual? As part of this project, a search for benign infections will be carried out in order to study the disease and the infecting hantavirus. Virus-reli interactions and the pathogenesis of hcps will be studied based on detection of cytokines and genetic markers, a recombinant n protein of Araraquara virus will be produced to be used in diagnostic methods and as a vaccine candidate. The virologists of the school of medicine of Ribeirão Preto have recently moved into a brand new virus research unit building. They look forward a support of fapesp in order to work together on the above mentioned research projects. (AU)

Scientific publications

(10)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FIGUEIREDO, L. T. M.; MORELI, M. L.; BORGES, A. A.; FIGUEIREDO, G. G.; SOUZA, R. L. M.; AQUINO, V. H.. Expression of a hantavirus N protein and its efficacy as antigen in immune assays. Brazilian Journal of Medical and Biological Research, v. 41, n. 7, p. 596-599, JUL 2008. (03/03682-3)

AQUINO, VICTOR H.; ANATRIELLO, ELEN; GONÇALVES, PAULA F.; SILVA, ELIANA V. DA; VASCONCELOS, PEDRO F. C.; VIEIRA, DEUSYLENE S.; BATISTA, WEBER C.; BOBADILLA, MARIA L.; VAZQUEZ, CYNTHIA; MORAN, MIRIAN; et al. Molecular epidemiology of dengue type 3 virus in Brazil and Paraguay, 2002-2004. American Journal of Tropical Medicine and Hygiene, v. 75, n. 4, p. 710-715, 2006. (03/03682-3)

LIVONESI, MÁRCIA C.; SOUSA, RICARDO L. MORO DE; BADRA, SORAYA J.; FIGUEIREDO, LUIZ T. M.. In vitro and in vivo studies of ribavirin action on Brazilian orthobunyavirus. American Journal of Tropical Medicine and Hygiene, v. 75, n. 5, p. 1011-1016, Nov. 2006. (03/03682-3)

SANTOS, RODRIGO I. M.; RODRIGUES, ALCIR H.; SILVA, MARIA LUCIA; MORTARA, RENATO A.; ROSSI, MARCOS A.; JAMUR, MARIA CELIA; OLIVER, CONSTANCE; ARRUDA, EURICO. Oropouche virus entry into HeLa cells involves clathrin and requires endosomal acidification. VIRUS RESEARCH, v. 138, n. 1-2, p. 139-143, DEC 2008. (03/03682-3)

MONDINI, ADRIANO; BRONZONI, ROBERTA VIEIRA DE MORAIS; CARDEAL, IZABELA LÍDIA SOARES; SANTOS, THAYZA MARIA ISABEL LOPES DOS; LÁZARO, EDUARDO; NUNES, SILVIA HELENA PEREIRA; SILVA, GISLAINE CELESTINO DUTRA; MADRID, MARIA CAROLINA FERRARI SARKIS; RAHAL, PAULA; FIGUEIREDO, LUIZ TADEU; et al. Simultaneous infection by DENY 3 and SLEV in Brazil. Journal of Clinical Virology, v. 40, n. 1, p. 84-86, Sept. 2007. (06/01070-9, 03/03682-3)

LIVONESI, MÁRCIA CRISTINA; SOUSA, RICARDO LUIZ MORO DE; FIGUEIREDO, LUIZ TADEU MORAES. In vitro study of antiviral activity of mycophenolic acid on Brazilian Orthobunyaviruses. Intervirology, v. 50, n. 3, p. 204-208, Apr. 2007. (03/03682-3)

LIVONESI, MÁRCIA CRISTINA; SOUSA, RICARDO LUIZ MORO DE; BADRA, SORAYA JABUR; FIGUEIREDO, LUIZ TADEU MORAES. In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus. Antiviral Research, v. 75, n. 2, p. 121-128, Aug. 2007. (03/03682-3)

MONDINI‚ A.; CARDEAL‚ I.L.S.; LÁZARO‚ E.; NUNES‚ S.H.; MOREIRA‚ C.C.; RAHAL‚ P.; MAIA‚ I.L.; FRANCO‚ C.; GÓNGORA‚ D.V.N.; GÓNGORA-RUBIO‚ F.; et al. Saint Louis encephalitis virus‚ Brazil. Emerging Infectious Diseases, v. 13, n. 1, p. 176, 2007. (03/03682-3)

SANTOS‚ R.I.M.; RODRIGUES‚ A.H.; SILVA‚ M.L.; MORTARA‚ R.A.; ROSSI‚ M.A.; JAMUR‚ M.C.; OLIVER‚ C.; ARRUDA‚ E.. Oropouche virus entry into HeLa cells involves clathrin and requires endosomal acidification. VIRUS RESEARCH, v. 138, n. 1, p. 139-143, 2008. (03/03682-3)

BORGES, ALESSANDRA ABEL; DONADI, EDUARDO ANTONIO; CAMPOS, GELSE MAZZONI; DE FIGUEIREDO, GLAUCIANE GARCIA; SAGGIORO, FABIANO PINTO; BADRA, SORAYA JABUR; SALOUM DEGHAIDE, NEIFI HASSAN; MORAES FIGUEIREDO, LUIZ TADEU. Polymorphisms in Human Leukocyte Antigens, Human Platelet Antigens, and Cytokine Genes in Hantavirus Cardiopulmonary Syndrome Patients from Ribeirao Preto, Brazil. Journal of Medical Virology, v. 86, n. 11, p. 1962-1970, NOV 2014. (03/03682-3)