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Pathogenesis and neurovirulence of emerging viruses in Brazil

Grant number: 16/00194-8
Support type:Research Grants - Young Investigators Grants
Duration: February 01, 2017 - January 31, 2021
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:José Luiz Proença Módena
Grantee:José Luiz Proença Módena
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Assoc. researchers: André Ricardo Ribas de Freitas ; Fabio Trindade Maranhão Costa ; Marco Aurélio Ramirez Vinolo ; Mariângela Ribeiro Resende ; Renata Sesti Costa ; Renato Passini Júnior ; Rodrigo Nogueira Angerami
Associated scholarship(s):18/10224-7 - The role of activation and metabolic imbalance of dendritic cells for Chikungunya Virus pathogenesis, BP.DR
17/26908-0 - The role of IRF-5 in Oropouche virus pathogenesis and neurovirulence, BP.DD
17/12957-9 - Zika virus and the placental barrier: the role of immune markers and cellular receptors on viral infection and activation of endothelial cells, BP.DD
17/02402-0 - The role of adaptive immune response in neuroinvasion by Oropouche and Zika virus, BP.MS

Abstract

Emerging viruses are agents associated with a new or a previous low-prevalent disease in a specific geographic region that significantly increased their incidence that area. Among the emerging viruses in Brazil is possible to highlight: Zika (ZIKV), Oropouche (OROV), Chikungunya (CHIKV), Mayaro (MAYV) and probably La Crosse (LACV), Iquitos virus (IQTV), Japanese Encephalitis (JEV), Saint Louis encephalitis (SLEV) and West Nile virus (WNV). These agents cause a wide spectrum of diseases in humans, from asymptomatic cases, rash febrile illness until severe clinical manifestations, such as neurological syndromes (Guillain-Barré syndrome, meningoencephalitis, flaccid paralysis among others) and congenital syndromes (abortion, fetal malformations, microcephaly, eye and hearing damage and other fetal manifestations). However, the pathogenetic factors associated with the development of these so different clinical outcomes are not completely understood, but it is known that viral replication, the type of infected cells and the immune response triggered early during infection are essential phenomena to the clinical results of a viral infectious process. Thus, the aim of this project is to characterize how cells and key components of the innate immune response, including pattern recognition receptors (TLR RIG, NLR, CGAS, Sting) and molecules induced by them (such as MyD88, IR-5) control the pathogenesis and neurovirulence ZIKV and OROV. For this, we will measure viral replication, immune cell activation and production of inflammatory mediators in patients, human and mice cells isolated in vitro (neutrophils, macrophages and myeloid and plasmacytoid dendritic cells) and wild-type and selected-knockouts (KO) mice infected with ZIKV and OROV. In order to obtain samples from naturally infected humans, this project will support an arbovirus surveillance network conducted by Unicamp since February 2016. This network has monitored patients treated in Campinas, including those with rash febrile illness (children, adults and pregnant women) and neurological manifestations possibly associated viral infection. The approval of this project will set up a referenced laboratory with biosafety-security level 2 (BSL-2) for arbovirus manipulation and detection at Biology Institute of Unicamp. This Lab will support the Universitary Hospital of Campinas and will allow the development of multidisciplinary researches with professors from Medical Science School of Unicamp. In addition, the present study has collaboration with researchers from Washington University in USA and A-Star Institute in Singapore. (AU)

Scientific publications (6)
(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)
KAM, YIU-WING; LEITE, JULIANA ALMEIDA; AMRUN, SITI NAQIAH; LUM, FOK-MOON; YEE, WEARN-XIN; ABU BAKAR, FARHANA; ENG, KAI ER; LYE, DAVID C.; LEO, YEE-SIN; CHONG, CHIA-YIN; RIBAS FREITAS, ANDRE RICARDO; MILANEZ, GUILHERME PAIER; PROENCA-MODENA, JOSE LUIZ; RENIA, LAURENT; COSTA, FABIO T. M.; NG, LISA F. P.; NETWORK, ZIKA-UNICAMP. ZIKV-Specific NS1 Epitopes as Serological Markers of Acute Zika Virus Infection. Journal of Infectious Diseases, v. 220, n. 2, p. 203-212, JUL 15 2019. Web of Science Citations: 1.
PROENCA-MODENA, JOSE LUIZ; CARDOSO, RICARDO DE SOUZA; CRIADO, MIRIA FERREIRA; MILANEZ, GUILHERME PAIER; DE SOUZA, WILLIAM MARCIEL; PARISE, PIERINA LORENCINI; BERTOL, JESSICA WILDGRUBE; SANTOS DE JESUS, BRUNA LAIS; MOREIRA PRATES, MIRELA CRISTINA; SILVA, MARIA LUCIA; BUZATTO, GUILHERME PIETRUCCI; DEMARCO, RICARDO CASSIANO; PEREIRA VALERA, FABIANA CARDOSO; TAMASHIRO, EDWIN; ANSELMO-LIMA, WILMA TEREZINHA; ARRUDA, EURICO. Human adenovirus replication and persistence in hypertrophic adenoids and palatine tonsils in children. Journal of Medical Virology, v. 91, n. 7, p. 1250-1262, JUL 2019. Web of Science Citations: 1.
PROENCA-MODENA, JOSE LUIZ; MILANEZ, GUILHERME PAIER; COSTA, MARIA LAURA; JUDICE, CARLA C.; MARANHAO COSTA, FABIO TRINDADE. Zika virus: lessons learned in Brazil. Microbes and Infection, v. 20, n. 11-12, p. 661-669, DEC 2018. Web of Science Citations: 5.
MOTTIN, MELINA; BORBA, JOYCE V. V. B.; BRAGA, RODOLPHO C.; TORRES, PEDRO H. M.; MARTINI, MATHEUS C.; PROENCA-MODENA, JOSE LUIZ; JUDICE, CARLA C.; COSTA, FABIO T. M.; EKINS, SEAN; PERRYMAN, ALEXANDER L.; ANDRADE, CAROLINA HORTA. The A-Z of Zika drug discovery. DRUG DISCOVERY TODAY, v. 23, n. 11, p. 1833-1847, NOV 2018. Web of Science Citations: 5.
JUDICE, CARLA CRISTINA; TAN, JESLIN J. L.; PARISE, PIERINA LORENCINI; KAM, YIU-WING; MILANEZ, GUILHERME PAIER; LEITE, JULIANA ALMEIDA; CASERTA, LEONARDO CARDIA; ARNS, CLARICE WEIS; RESENDE, MARIANGELA RIBEIRO; ANGERAMI, RODRIGO; AMARAL, ELIANA; PASSINI JUNIOR, RENATO; RIBAS FREITAS, ANDRE RICARDO; MARANHAO COSTA, FABIO TRINDADE; PROENCA-MODENA, JOSE LUIZ; NG, LISA F. P.; NETWORK, ZIKA-UNICAMP. Efficient detection of Zika virus RNA in patients' blood from the 2016 outbreak in Campinas, Brazil. SCIENTIFIC REPORTS, v. 8, MAR 5 2018. Web of Science Citations: 6.
KAM, YIU-WING; LEITE, JULIANA ALMEIDA; LUM, FOK-MOON; TAN, JESLIN J. L.; LEE, BERNETT; JUDICE, CARLA C.; DE TOLEDO TEIXEIRA, DANIEL AUGUSTO; ANDREATA-SANTOS, ROBERT; VINOLO, MARCO A.; ANGERAMI, RODRIGO; RESENDE, MARIANGELA RIBEIRO; RIBAS FREITAS, ANDRE RICARDO; AMARAL, ELIANA; PASSINI JUNIOR, RENATO; COSTA, MARIA LAURA; GUIDA, JOSE PAULO; ARNS, CLARICE WEIS; FERREIRA, LUIS CARLOS S.; NIA, LAURENT R.; PROENCA-MODENA, JOSE LUIZ; NG, LISA F. P.; COSTA, FABIO T. M.; NETWORK, ZIKA-UNICAMP. Specific Biomarkers Associated With Neurological Complications and Congenital Central Nervous System Abnormalities From Zika Virus-Infected Patients in Brazil. Journal of Infectious Diseases, v. 216, n. 2, p. 172-181, JUL 15 2017. Web of Science Citations: 19.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.