Pathogenesis and neurovirulence of emerging viruses in Brazil

• Grant number: 16/00194-8
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: February 01, 2017 - April 30, 2021
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: José Luiz Proença Módena
• Grantee: José Luiz Proença Módena
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated 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 grant(s): 20/04558-0 - Characterization of intrinsic risk factors and the development of new diagnostic and treatment alternatives for COVID-19, AP.R
• 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; 17/22062-9 - Arbovirus detection and characterization in Campinas, BP.TT; 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

(27)

(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)

SILVA-FILHO, JOAO LUIZ; DE OLIVEIRA, LILIAN G.; MONTEIRO, LETICIA; PARISE, PIERINA L.; ZANLUQUI, NAGELA G.; POLONIO, CAROLINA M.; DE FREITAS, CARLA L.; TOLEDO-TEIXEIRA, DANIEL A.; DE SOUZA, WILLIAM M.; BITTENCOURT, NAJARA; et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. BRAIN BEHAVIOR AND IMMUNITY, v. 97, p. 260-274, OCT 2021. (17/26908-0, 16/00194-8, 20/02159-0, 16/21259-0, 18/13866-0, 16/12855-9, 17/22062-9, 17/26170-0, 17/11828-0, 17/02402-0, 20/02448-2, 18/13645-3, 16/07371-2)

AMORIM, MARIENE RIBEIRO; PONTELLI, MARJORIE CORNEJO; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; TOLEDO-TEIXEIRA, DANIEL A.; FORATO, JULIA; BISPO-DOS-SANTOS, KARINA; BARBOSA, NATALIA S.; MARTINI, MATHEUS CAVALHEIRO; PARISE, PIERINA LORENCINI; et al. Oropouche Virus Infects, Persists and Induces IFN Response in Human Peripheral Blood Mononuclear Cells as Identified by RNA PrimeFlow (TM) and qRT-PCR Assays. Viruses-Basel, v. 12, n. 7, JUL 2020. (16/00194-8)

AMORIM, MARIENE R.; SOUZA, WILLIAM M.; BARROS, JR., ANTONIO C. G.; TOLEDO-TEIXEIRA, DANIEL A.; BISPO-DOS-SANTOS, KARINA; SIMEONI, CAMILA L.; PARISE, PIERINA L.; VIEIRA, ALINE; FORATO, JULIA; CLARO, INGRA M.; et al. Respiratory Viral Shedding in Healthcare Workers Reinfected with SARS-CoV-2, Brazil, 2020. Emerging Infectious Diseases, v. 27, n. 6, p. 1737-1740, JUN 2021. (20/04558-0, 16/00194-8, 20/02448-2, 18/14389-0, 17/13981-0, 17/26908-0, 19/24251-9, 20/02159-0)

BAGNO, FLAVIA F.; ANDRADE, LUIS A. F.; SERGIO, SARAH A. R.; PARISE, PIERINA L.; TOLEDO-TEIXEIRA, DANIEL A.; GAZZINELLI, RICARDO T.; FERNANDES, ANA P. S. M.; TEIXEIRA, SANTUZA M. R.; GRANJA, FABIANA; PROENCA-MODENA, JOSE L.; et al. Previous Infection with SARS-CoV-2 Correlates with Increased Protective Humoral Responses after a Single Dose of an Inactivated COVID-19 Vaccine. Viruses-Basel, v. 14, n. 3, p. 9-pg., 2022-03-01. (16/00194-8, 20/04558-0)

CARMO, HELISON RAFAEL P.; YOSHINAGA, MARCOS Y.; CASTILLO, ALEJANDRO ROSELL; CHAVES-FILHO, ADRIANO BRITTO; BONILHA, ISABELLA; BARRETO, JOAQUIM; MURARO, STEFANIE PRIMON; DE SOUZA, GABRIELA FABIANO; DAVANZO, GUSTAVO GASTAO; PERROUD JR, MAURICIO W.; et al. Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19. MOLECULAR GENETICS AND METABOLISM, v. 138, n. 4, p. 8-pg., 2023-03-06. (20/04558-0, 20/12649-5, 16/00194-8, 13/07937-8, 18/17792-0)

BRUNETTI, NATALIA S.; DAVANZO, GUSTAVO G.; DE MORAES, DIOGO; FERRARI, ALLAN J. R.; SOUZA, GABRIELA F.; MURARO, STEFANIE PRIMON; KNITTEL, THIAGO L.; BOLDRINI, VINICIUS O.; MONTEIRO, LAUAR B.; VIRGILIO-DA-SILVA, JOO VICTOR; et al. SARS-CoV-2 uses CD4 to infect T helper lymphocytes. eLIFE, v. 12, p. 26-pg., 2023-07-31. (20/04558-0, 15/15626-8, 19/06459-1, 19/04726-2, 19/16116-4, 19/05155-9, 19/13552-8, 16/18031-8, 19/00098-7, 20/04583-4, 16/00194-8, 21/08354-2, 19/17007-4, 19/22398-2, 17/01184-9, 19/14465-1, 20/04579-7, 13/08293-7, 18/14933-2, 17/23920-9, 19/06372-3, 16/24163-4, 16/23328-0, 20/04919-2, 20/04746-0)

VENCESLAU, EMANUELLA MENESES; GUIDA, JOSE PAULO; AMARAL, ELIANA; PROENCA MODENA, JOSE LUIS; COSTA, MARIA LAURA. Characterization of Placental Infection by Zika Virus in Humans: A Review of the Literature. Revista Brasileira de Ginecologia e Obstetrícia, v. 42, n. 9, p. 577-585, SEP 2020. (16/00194-8)

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; et al. 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. (16/00194-8, 13/25807-4)

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; et al. 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. (16/00194-8, 09/51818-8)

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; et al. Efficient detection of Zika virus RNA in patients' blood from the 2016 outbreak in Campinas, Brazil. SCIENTIFIC REPORTS, v. 8, MAR 5 2018. (16/00194-8)

SACCON, TATIANA DANDOLINI; MOUSOVICH-NETO, FELIPPE; LUDWIG, RAISSA GUIMARAES; CARREGARI, VICTOR CORASOLLA; DOS ANJOS SOUZA, ANA BEATRIZ; DOS PASSOS, AMANDA STEPHANE CRUZ; MARTINI, MATHEUS CAVALHEIRO; BARBOSA, PRISCILLA PASCHOAL; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; et al. SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner. NATURE COMMUNICATIONS, v. 13, n. 1, p. 15-pg., 2022-09-29. (20/08716-9, 20/04558-0, 19/05155-9, 21/10373-5, 13/07607-8, 20/04919-2, 20/04746-0, 17/01184-9, 17/23920-9, 16/24163-4, 16/00194-8, 18/21635-8, 19/00098-7, 20/05040-4, 17/08264-8, 20/04579-7, 19/26119-0, 19/04726-2, 20/04583-4, 20/15959-5)

ANDRADE, LUIS A. F.; BAGNO, FLAVIA F.; SERGIO, SARAH A. R.; PARISE, PIERINA L.; TOLEDO-TEIXEIRA, DANIEL A.; FERNANDES, ANA P. S. M.; TEIXEIRA, SANTUZA M. R.; GRANJA, FABIANA; PROENCA-MODENA, JOSE LUIZ; DA FONSECA, FLAVIO G.. Heterogeneity of humoral response patterns in mildly symptomatic, non-hospitalized COVID-19 patients: A one-year longitudinal study. Experimental Biology and Medicine, v. 248, n. 10, p. 9-pg., 2023-03-20. (16/00194-8, 20/04558-0)

BARRETO, ESTER A.; CRUZ, AMANDA S.; VERAS, FLAVIO P.; MARTINS, RONALDO; BERNARDELLI, RAFAELLA S.; PAIVA, ISADORA M.; LIMA, THAIS M.; SINGH, YOUVIKA; GUIMARAES, RAPHAEL C.; DAMASCENO, SAMARA; et al. COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 120, n. 21, p. 10-pg., 2023-05-15. (16/00194-8, 20/05040-4, 17/08264-8, 20/04558-0)

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. (16/00194-8)

RIBEIRO, LUCIANA C.; BENITES, BRUNO DELTREGGIA; ULAF, RAISA G.; NUNES, THYAGO A.; COSTA-LIMA, CAROLINA; ADDAS-CARVALHO, MARCELO; PROENCA-MODENA, JOSE LUIZ; GRANJA, FABIANA; DA COSTA, VITOR ANTONIO; SANTOS DUARTE, ADRIANA DA SILVA; et al. Rapid clinical recovery of a SARS-CoV-2 infected common variable immunodeficiency patient following the infusion of COVID-19 convalescent plasma. ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY, v. 17, n. 1, DEC 5 2021. (20/04558-0, 20/04522-5, 13/07607-8, 16/00194-8)

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; et al. 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. (16/00194-8)

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.; et al. The A-Z of Zika drug discovery. DRUG DISCOVERY TODAY, v. 23, n. 11, p. 1833-1847, NOV 2018. (12/16525-2, 16/00194-8, 17/02353-9, 16/13805-5)

CANDIDO, DARLAN S.; CLARO, INGRA M.; DE JESUS, JAQUELINE G.; SOUZA, WILLIAM M.; MOREIRA, FILIPE R. R.; DELLICOUR, SIMON; MELLAN, THOMAS A.; DU PLESSIS, LOUIS; PEREIRA, RAFAEL H. M.; SALES, FLAVIA C. S.; et al. Evolution and epidemic spread of SARS-CoV-2 in Brazil. Science, v. 369, n. 6508, SI, p. 1255+, SEP 4 2020. (20/04558-0, 16/00194-8, 19/21301-5, 18/14389-0, 18/14933-2, 17/13981-0, 20/04836-0, 18/25468-9, 16/18445-7, 18/09383-3, 18/17176-8, 19/12000-1, 19/07544-2, 19/24251-9)

BORIN, ALEXANDRE; COIMBRA, LAIS D.; BISPO-DOS-SANTOS, KARINA; NACIUK, FABRICIO F.; FONTOURA, MARINA; SIMEONI, CAMILA L.; GOMES, GIOVANNI, V; AMORIM, MARIENE R.; GRAVINA, HUMBERTO D.; SHIMIZU, JACQUELINE FARINHA; et al. Identification and characterization of the anti-SARS-CoV-2 activity of cationic amphiphilic steroidal compounds. VIRULENCE, v. 13, n. 1, p. 18-pg., 2022-12-31. (20/04558-0, 16/00194-8, 19/06459-1)

SABINO, JANINE S.; AMORIM, MARIENE R.; DE SOUZA, WILLIAM M.; MAREGA, LIA F.; MOFATTO, LUCIANA S.; TOLEDO-TEIXEIRA, DANIEL A.; FORATO, JULIA; STABELI, RODRIGO G.; COSTA, MARIA LAURA; SPILKI, FERNANDO R.; et al. Clearance of Persistent SARS-CoV-2 RNA Detection in a NF kappa B-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report. Viruses-Basel, v. 14, n. 5, p. 10-pg., 2022-05-01. (20/04558-0, 18/14389-0, 16/00194-8, 18/14372-0)

NOBREGA, GUILHERME M.; SAMOGIM, ANA PAULA; PARISE, PIERINA L.; VENCESLAU, EMANUELLA M.; GUIDA, JOSE PAULO S.; JAPECANGA, RODOLFO R.; AMORIM, MARIENE R.; TOLEDO-TEIXEIRA, DANIEL A.; FORATO, JULIA; CONSONNI, SILVIO R.; et al. TAM and TIM receptors mRNA expression in Zika virus infected placentas. Placenta, v. 101, p. 204-207, NOV 2020. (17/26908-0, 17/22062-9, 17/02402-0, 19/18720-6, 16/00194-8)

VENCESLAU, EMANUELLA MENESES; SIQUEIRA GUIDA, JOSE PAULO; NOBREGA, GUILHERME DE MORAES; SAMOGIM, ANA PAULA; PARISE, PIERINA LORENCINI; JAPECANGA, RODOLFO ROSA; DE TOLEDO-TEIXEIRA, DANIEL AUGUSTO; FORATO, JULIA; ANTOLINI-TAVARES, ARTHUR; SOUZA, ARETHUSA; et al. Adequate Placental Sampling for the Diagnosis and Characterization of Placental Infection by Zika Virus. FRONTIERS IN MICROBIOLOGY, v. 11, FEB 21 2020. (17/26908-0, 16/00194-8, 17/02402-0)

SALGADO, BARBARA BATISTA; MAUES, FABIO CARMONA DE JESUS; JORDAO, MAELE; PEREIRA, RENATO LEMOS; TOLEDO-TEIXEIRA, DANIEL A.; PARISE, PIERINA L.; GRANJA, FABIANA; SOUZA, HIGO FERNANDO SANTOS; YAMAMOTO, MARCIO MASSAO; CHIANG, JANNIFER OLIVEIRA; et al. Antibody cross-reactivity and evidence of susceptibility to emerging Flaviviruses in the dengue-endemic Brazilian Amazon. INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, v. 129, p. 10-pg., 2023-02-21. (16/00194-8, 20/04558-0)

SALA ELPIDIO, LAISE NAYANA; DE MORAES, AMARILIS GIARETTA; VOLKWEIS LANGER, IEDA BERNADETE; DO AMARAL, GREICY CEZAR; MORETTI, MARIA LUIZA; GARCIA, MARCIA TEIXEIRA; ANGERAMI, RODRIGO; PROENCA-MODENA, JOSE LUIZ; BISPO-DOS-SANTOS, KARINA; MARTINI, MATHEUS CAVALHEIRO; et al. Lack of association of the KIR and HLA class I ligands with ZIKV infection in south and southeast of Brazil. Memórias do Instituto Oswaldo Cruz, v. 117, p. 9-pg., 2022-01-01. (16/00194-8, 16/05115-9)

RIBEIRO, LUCIANA C.; BENITES, BRUNO DELTREGGIA; ULAF, RAISA G.; NUNES, THYAGO A.; COSTA-LIMA, CAROLINA; ADDAS-CARVALHO, MARCELO; PROENCA-MODENA, JOSE LUIZ; GRANJA, FABIANA; DA COSTA, VITOR ANTONIO; SANTOS DUARTE, ADRIANA DA SILVA; et al. Rapid clinical recovery of a SARS-CoV-2 infected common variable immunodeficiency patient following the infusion of COVID-19 convalescent plasma. ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY, v. 17, n. 1, p. 4-pg., 2021-02-05. (13/07607-8, 16/00194-8, 20/04522-5, 20/04558-0)

DE SOUZA, WILLIAM M.; MURARO, STEFANIE P.; SOUZA, GABRIELA F.; AMORIM, MARIENE R.; SESTI-COSTA, RENATA; MOFATTO, LUCIANA S.; FORATO, JULIA; BARBOSA, PRISCILLA P.; TOLEDO-TEIXEIRA, DANIEL A.; BISPO-DOS-SANTOS, KARINA; et al. lusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccine. Viruses-Basel, v. 13, n. 11, NOV 2021. (16/00194-8, 18/14389-0, 18/13645-3, 17/26908-0, 20/02159-0, 17/13981-0, 19/09704-7, 18/10224-7, 19/24251-9, 20/04558-0)

LIMA, CAROLINE SPRENGEL; MOTTIN, MELINA; DE ASSIS, LETICIA RIBEIRO; DE MORAES ROSO MESQUITA, NATHALYA CRISTINA; DE PAULA SOUSA, BRUNA KATIELE; COIMBRA, LAIS DURCO; BISPO-DOS-SANTOS, KARINA; ZORN, KIMBERLEY M.; GUIDO, RAFAEL V. C.; EKINS, SEAN; et al. Flavonoids from Pterogyne nitens as Zika virus NS2B-NS3 protease inhibitors. BIOORGANIC CHEMISTRY, v. 109, APR 2021. (16/00194-8, 18/03917-6, 13/07600-3, 14/18330-0, 18/15083-2)