Studies with Bunyaviridae that produce human disease

• Grant number: 14/02438-6
• Support Opportunities: Research Projects - Thematic Grants
• Duration: April 01, 2015 - August 31, 2020
• 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 ; Luis Lamberti Pinto da Silva
• Associated grant(s): 19/02418-9 - Molecular mechanisms of Oropouche Virus assembly, AP.R; 18/50016-4 - Experimental infection of neotropical bats with Hantavirus, AP.R SPRINT
• Associated scholarship(s): 19/20193-4 - Study of the involvement of ESCRT machinery in the assembly and budding of zika virus in human glioblastoma cells, BP.MS; 19/08461-3 - Study of Oropouche virus assembly mechanism in neurons and its effects on the cellular proteostasis, BP.MS; 19/07443-1 - Investigation on hantavirus and other virus (Bunyaviridae) in small mammals and their ectoparasites, BP.PD; + associated scholarships 16/25763-5 - An eco-epidemiological study of the Zika Virus in the Northeastern Region of the State of São Paulo, BP.DR; 18/19469-2 - Analysis of ESCRT machinery participation in the replicative cycle of the Zika Virus in human cells, BP.IC; 18/09383-3 - Study about Flavivirus epitopes with medical importance in Brazil and its antibodies, BP.DR; 18/03067-2 - Construction of recombinant plasmids to identify sorting and subcellular localization signals in the glycoproteins of Oropouche virus, BP.TT; 17/13981-0 - Characterization, genomics and diagnostic of viruses with importance for public health in Brazil by high throughput sequencing, BP.PD; 16/06490-8 - The role of placental exosomes and microRNAs in the protection against the arboviruses Zika, Chikungunya and Oropouche, BP.DD; 16/18356-4 - Study of host cellular factors involved in assembly and budding of Orthobunyavirus using Oropouche virus as a model, BP.DD; 16/17457-1 - Compounds screening with potential antiviral action against Alphaviruses and Orthobunyaviruses, BP.DR; 16/05945-1 - Mechanisms involved in the assembly and externalization of Zika virus in human cells., BP.MS; 16/02568-2 - Research on hantavirus and other viruses in wild small mammals and their ectoparasites, BP.PD; 16/01414-1 - Production of recombinant viral antigenic peptides and development of methods for serological diagnosis of infections by Chikungunya, Mayaro and Zika viruses, BP.MS; 15/26667-7 - Identification of organelles and cellular factors involved in the assembly and budding of Araraquara hantavirus (ARAQV), BP.PD; 15/05354-0 - Functional analysis of the M segment non-structural protein (NSm) of Orthobunyavirus Oropouche, BP.DR - associated scholarships

Abstract

This thematic Project includes 29 subprojects, focusing on emerging zoonotic viruses of the family Bunyaviridae, distributed in 3 genera: Orthobunyavirus, Phlebovirus and Hantavirus. The project involves 3 Principal Researchers, 55 Brazilian and international collaborators, and will take 4 years. For studies on the genus Orthobunyavirus, serological diagnosis of Oropouche virus (OROV) by ELISA will be developed using a recombinant N protein of OROV as antigen. This will enable sero-epidemiological surveys in patients, horses, small mammals and birds. The recombinant N protein of OROV will also be tested as an immunogen in mice, and the mechanism of its apoptotic effect will be studied in vitro. The antiviral activity of 10,000 compounds for Orthobunyavirus will be tested. Cell biology in vitro studies will be done to verify sites of OROV assembly and budding in host cells, and to identify factors that regulate intracellular traffic of proteins involved in those processes. A fluorescent OROV will also be produced by reverse genetics for in vitro and in vivo studies. Molecular epidemiology and phylogenetic studies of orthobunyaviruses based on complete genomes will be done by next-generation sequencing. A real time RT-PCR assay for detection of Brazilian orthobunyaviruses of serogroups C and Simbu will also be developed. Studies on the genus Phlebovirus will include molecular epidemiology and phylogeny, development of a real time RT-PCR to assess their occurrence in clinical samples from patients with acute febrile illness, testing of the antiviral activity of of 10,000 compounds and development of an experimental mouse model of infection by Candiru virus. Studies will also be done to detect assembly/budding sites of Candiru virus. Studies on the genus Hantavirus will include virus detection in hantavirus cardio-pulmonary syndrome (HCPS) and study of its pathophysiology based on levels of cytokines in patient blood samples. Importantly, we plan to characterize genetically and morphologically the Araraquara (ARQV) strain of antavirus and evaluate the immunogenicity of a recombinant N protein of ARQV in mice. We also will test the antiviral activity of 10,000 compounds against The strain Rio Mamore of hantavirus). Field capture of small mammals and their ectoparasites will be done to investigate Hantavirus infection, especially in Necromys lasiurus. A molecular epidemiology study will be done in cooperation with scientists from other national and international (USA, Finland and Colombia) institutions, based on computational analysis of the evolution and geographical distribution of Brazilian hantaviruses. Cell biology studies will hopefully reveal details of Hantavirus assembly and budding. (AU)

Scientific publications

(23)

(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)

SABINO-SANTOS, JR., GILBERTO; MOTTA MAIA, FELIPE GONCALVES; MARTINS, RONALDO BRAGANCA; GAGLIARDI, TALITA BIANCA; DE SOUZA, WILLIAM MARCIEL; MUYLAERT, RENATA LARA; DE SOUZA LUNA, LUCIANO KLEBER; MELO, DANILO MACHADO; CARDOSO, RICARDO DE SOUZA; BARBOSA, NATALIA DA SILVA; et al. Natural infection of Neotropical bats with hantavirus in Brazil. SCIENTIFIC REPORTS, v. 8, JUN 13 2018. (12/24150-9, 11/06810-9, 11/19897-5, 11/22663-6, 16/02568-2, 12/03700-0, 14/02438-6, 15/05354-0, 15/06142-7, 13/06380-0, 12/04096-0)

PEREIRA, ESTELA A.; DASILVA, LUIS L. P.. HIV-1 Nef: Taking Control of Protein Trafficking. TRAFFIC, v. 17, n. 9, p. 976-996, SEP 2016. (14/02438-6, 14/25812-0)

BARBOSA, NATALIA S.; MENDONCA, LEILA R.; DIAS, MARCOS V. S.; PONTELLI, MARJORIE C.; DA SILVA, ELAINE Z. M.; CRIADO, MIRIA F.; DA SILVA-JANUARIO, MARA E.; SCHINDLER, MICHAEL; JAMUR, MARIA C.; OLIVER, CONSTANCE; et al. ESCRT machinery components are required for Orthobunyavirus particle production in Golgi compartments. PLOS PATHOGENS, v. 14, n. 5, MAY 2018. (14/02438-6, 09/54014-7, 14/25812-0)

DE SOUZA, WILLIAM MARCIEL; ACRANI, GUSTAVO OLSZANSKI; ROMEIRO, MARILIA FARIGNOLI; REIS JUNIOR, OSVALDO; TOLARDO, ALINE LAVADO; SERRAO DE ANDRADE, AMANDA ARAUJO; GONCALVES VIANEZ JUNIOR, JOAO LIDIO DA SILVA; DE ALMEIDA MEDEIROS, DANIELE BARBOSA; TEIXEIRA NUNES, MARCIO ROBERTO; MORAES FIGUEIREDO, LUIZ TADEU. Complete genome sequence of Piry vesiculovirus. ARCHIVES OF VIROLOGY, v. 161, n. 8, p. 2325-2328, AUG 2016. (12/24150-9, 13/14929-1, 14/20851-8, 13/02256-2, 14/02438-6, 15/05778-5)

DE SOUZA, WILLIAM MARCIEL; ACRANI, GUSTAVO OLSZANSKI; ROMEIRO, MARILIA FARIGNOLI; REIS, JR., OSVALDO; TOLARDO, ALINE LAVADO; DA SILVA, SANDRO PATROCA; DE ALMEIDA MEDEIROS, DANIELE BARBOSA; VARELA, MARIANA; TEIXEIRA NUNES, MARCIO ROBERTO; MORAES FIGUEIREDO, LUIZ TADEU. Molecular characterization of Capim and Enseada orthobunyaviruses. INFECTION GENETICS AND EVOLUTION, v. 40, p. 47-53, JUN 2016. (15/05778-5, 12/24150-9, 13/14929-1, 14/02438-6, 14/20851-8)

DE SOUZA LUNA, LUCIANO KLEBER; RODRIGUES, ALCIR HUMBERTO; MARQUES SANTOS, RODRIGO IVO; SESTI-COSTA, RENATA; CRIADO, MIRIA FERREIRA; MARTINS, RONALDO B.; SILVA, MARIA LUCIA; DELCARO, LUANA SELLA; PROENCA-MODENA, JOSE LUIZ; MORAES FIGUEIREDO, LUIZ TADEU; et al. Oropouche virus is detected in peripheral blood leukocytes from patients. Journal of Medical Virology, v. 89, n. 6, p. 1108-1111, JUN 2016. (14/02438-6)

AMARILLA, ALBERTO A.; SANTOS-JUNIOR, NILTON NASCIMENTO; FIGUEIREDO, MARIO LUIS; MESQUITA LUIZ, JOAO PAULO; FUMAGALLI, MARCILIO JORGE; COLON, DAVID F.; LIPPI, VERONICA; ALFONSO, HELDA LIZ; LIMA-JUNIOR, DJALMA S.; TRABUCO, AMANDA C.; et al. CCR2 Plays a Protective Role in Rocio Virus-Induced Encephalitis by Promoting Macrophage Infiltration Into the Brain. Journal of Infectious Diseases, v. 219, n. 12, p. 2015-2025, JUN 15 2019. (12/11169-3, 12/08778-8, 14/15548-4, 14/02438-6)

TAVARES, LUCAS A.; DA SILVA, EULALIA M. L.; DA SILVA-JANUARIO, MARA E.; JANUARIO, YUNAN C.; DE CAVALHO, JULIANNE V.; CZERNISZ, ERIKA S.; MARDONES, GONZALO A.; DASILVA, LUIS L. P.. CD4 downregulation by the HIV-1 protein Nef reveals distinct roles for the gamma 1 and gamma 2 subunits of the AP-1 complex in protein trafficking. Journal of Cell Science, v. 130, n. 2, p. 429-443, JAN 15 2017. (14/02438-6, 09/54014-7, 14/25812-0)

FUMAGALLI, MARCILIO JORGE; DE SOUZA, WILLIAM MARCIEL; ROMEIRO, MARILIA FARIGNOLI; DE SOUZA COSTA, MICHELL CHARLES; SLHESSARENKO, RENATA DEZENGRINI; MORAES FIGUEIREDO, LUIZ TADEU. Development of an Enzyme-Linked Immunosorbent Assay To Detect Antibodies Targeting Recombinant Envelope Protein 2 of Mayaro Virus. Journal of Clinical Microbiology, v. 57, n. 5, MAY 2019. (12/24150-9, 17/13981-0, 16/01414-1, 14/02438-6, 14/20851-8)

FUMAGALLI, MARCILIO JORGE; DE SOUZA, WILLIAM MARCIEL; ALVES ESPOSITO, DANILLO LUCAS; SILVA, ANGELICA; ROMEIRO, MARILIA FARIGNOLI; MARTINEZ, EDSON ZANGIACOMI; LOPES DA FONSECA, BENEDITO ANTONIO; MORAES FIGUEIREDO, LUIZ TADEU. Enzyme-linked immunosorbent assay using recombinant envelope protein 2 antigen for diagnosis of Chikungunya virus. VIROLOGY JOURNAL, v. 15, JUL 24 2018. (16/01414-1, 14/02438-6, 12/24150-9, 17/13981-0, 14/20851-8)

DE MELO JUNIOR, ARISTIDES BEZERRA; DE SOUZA, WILLIAM MARCIEL; ACRANI, GUSTAVO OLSZANSKI; CARVALHO, VALERIA LIMA; ROMEIRO, MARILIA FARIGNOLI; TOLARDO, ALINE LAVADO; DA SILVA, SANDRO PATROCA; CARDOSO, JEDSON FERREIRA; CHIANG, JANNIFER DE OLIVEIRA; DA SILVA GONCALVES VIANEZ JUNIOR, JOAO LIDIO; et al. Genomic characterization and evolution of Tacaiuma orthobunyavirus (Peribunyaviridae family) isolated in Brazil. INFECTION GENETICS AND EVOLUTION, v. 60, p. 71-76, JUN 2018. (12/24150-9, 17/13981-0, 14/02438-6, 14/20851-8, 16/17457-1)

AMARILLA, ALBERTO ANASTACIO; FUMAGALLI, MARCILIO JORGE; FIGUEIREDO, MARIO LUIS; LIMA-JUNIOR, DJALMA S.; SANTOS-JUNIOR, NILTON NASCIMENTO; ALFONSO, HELDA LIZ; LIPPI, VERONICA; TRABUCO, AMANDA CRISTINA; LAURETTI, FLAVIO; MULLER, VANESSA DANIELLE; et al. Ilheus and Saint Louis encephalitis viruses elicit cross-protection against a lethal Rocio virus challenge in mice. PLoS One, v. 13, n. 6, JUN 13 2018. (12/08778-8, 14/15548-4, 14/02438-6)

NUNES-NETO, JOAQUIM PINTO; DE SOUZA, WILLIAM MARCIEL; ACRANI, GUSTAVO OLSZANSKI; ROMEIRO, MARILIA FARIGNOLI; FUMAGALLI, MARCILIOJORGE; VIEIRA, LUIZ CARLOS; DE ALMEIDA MEDEIROS, DANIELE BARBOSA; LIMA, JULIANA ABREU; SILVA DE LIMA, CLAYTON PEREIRA; CARDOSO, JEDSON FERREIRA; et al. Characterization of the Bujaru, frijoles and Tapara antigenic complexes into the sandfly fever group and two unclassified phleboviruses from Brazil. JOURNAL OF GENERAL VIROLOGY, v. 98, n. 4, p. 585-594, APR 2017. (15/05778-5, 12/24150-9, 13/14929-1, 16/01414-1, 14/02438-6, 14/20851-8)

TAVARES, LUCAS A.; DE CARVALHO, V, JULIANNE; COSTA, CRISTINA S.; SILVEIRA, ROBERTA M.; DE CARVALHO, ANDREIA N.; DONADI, EDUARDO A.; DASILVA, LUIS L. P.. Two Functional Variants of AP-1 Complexes Composed of either gamma 2 or gamma 1 Subunits Are Independently Required for Major Histocompatibility Complex Class I Downregulation by HIV-1 Nef. Journal of Virology, v. 94, n. 7, APR 2020. (16/05945-1, 16/18207-9, 15/26667-7, 14/02438-6, 18/08966-5, 18/00297-7)

SABINO-SANTOS JR, GILBERTO; FERREIRA, FRANCIMEIRE FERNANDES; FERREIRA DA SILVA, DAVID JOSE; MACHADO, DANILO MELO; DA SILVA, SERGIO GOMES; SAO BERNARDO, CHRISTINE STEINER; DOS SANTOS FILHO, MANOEL; LEVI, TAAL; MORAES FIGUEIREDO, LUIZ TADEU; PERES, CARLOS A.; et al. Hantavirus antibodies among phyllostomid bats from the arc of deforestation in Southern Amazonia, Brazil. TRANSBOUNDARY AND EMERGING DISEASES, v. 67, n. 3, DEC 2019. (14/02438-6, 16/02568-2)

ROMEIRO, MARILIA FARIGNOLI; FUMAGALLI, MARCILIO JORGE; DOS ANJOS SOUZA, ANA BEATRIZ; MORAES FIGUEIREDO, LUIZ TADEU. Serological evidence of Mayaro virus infection in blood donors from sao Carlos, sao Paulo, Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene, v. 114, n. 9, p. 693-696, SEP 2020. (14/20851-8, 16/01414-1, 14/02438-6)

CLOSOSKI, GIULIANO C.; SOLDI, RAFAEL A.; DA SILVA, RODRIGO M.; GUARATINI, THAIS; LOPES, JOSE N. C.; PEREIRA, PAMELA R. R.; LOPES, JOAO L. C.; DOS SANTOS, THIAGO; MARTINS, RONALDO B.; COSTA, CRISTINA S.; et al. Tenofovir Disoproxil Fumarate: New Chemical Developments and Encouraging in vitro Biological Results for SARS-CoV-2. Journal of the Brazilian Chemical Society, v. 31, n. 8, p. 1552-1556, AUG 2020. (14/50265-3, 18/14150-8, 14/02438-6)

DE SOUZA, WILLIAM MARCIE; FUMAGALLI, MARCILIO JORGE; TORRES CARRASCO, ADRIANO DE OLIVEIRA; ROMEIRO, MARILIA FARIGNOLI; MODHA, SEJAL; SEKI, MEIRE CHRISTINA; GHELLER, JANAINA MENEGAZZO; DAFFRE, SIRLEI; TEIXEIRA NUNES, MARCIO ROBERTO; MURCIA, PABLO RAMIRO; et al. Viral diversity of Rhipicephalus microplus parasitizing cattle in southern Brazil. SCIENTIFIC REPORTS, v. 8, NOV 5 2018. (16/01414-1, 14/02438-6, 15/05778-5, 13/14929-1, 12/24150-9, 17/13981-0, 14/20851-8)

DASILVA, LUIS L. P.. The Ambiguous Roles of Extracellular Vesicles in HIV Replication and Pathogenesis. FRONTIERS IN MICROBIOLOGY, v. 9, OCT 10 2018. (14/02438-6, 18/00297-7)

MORAES FIGUEIREDO, LUIZ TADEU. Human Urban Arboviruses Can Infect Wild Animals and Jump to Sylvatic Maintenance Cycles in South America. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 9, JUL 17 2019. (14/02438-6)

RUSSO, RAQUEL RINALDI; DOS SANTOS JUNIOR, NILTON NASCIMENTO; OLIVEIRA CINTRA, ADELIA CRISTINA; MORAES FIGUEIREDO, LUIZ TADEU; SAMPAIO, SUELY VILELA; AQUINO, VICTOR HUGO. Expression, purification and virucidal activity of two recombinant isoforms of phospholipase A(2) from Crotalus durissus terrificus venom. ARCHIVES OF VIROLOGY, v. 164, n. 4, p. 1159-1171, APR 2019. (14/02438-6, 12/12605-1)

COSTA BARREIRA, LUZIA APARECIDA; SCHEUCHER, PRISCILA SANTOS; ROMEIRO, MARILIA FARIGNOLI; LA SERRA, LEONARDO; BADRA, SORAYA JABUR; DE SOUZA, WILLIAM MARCIEL; MORAES FIGUEIREDO, LUIZ TADEU. Evaluating the use of fluorescence-based flow cytometry assay for dengue diagnosis using peripheral blood mononuclear cells. Revista da Sociedade Brasileira de Medicina Tropical, v. 51, n. 2, p. 168-173, MAR-APR 2018. (14/20851-8, 12/24150-9, 17/13981-0, 14/02438-6)

ALMEIDA, GLAUCIA M.; SOUZA, JULIANO P.; MENDES, NIELE D.; PONTELLI, MARJORIE C.; PINHEIRO, NATHALIA R.; NOGUEIRA, GIOVANNA O.; CARDOSO, RICARDO S.; PAIVA, ISADORA M.; FERRARI, GUSTAVO D.; VERAS, FLAVIO P.; et al. Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response. FRONTIERS IN NEUROSCIENCE, v. 15, NOV 23 2021. (14/02438-6, 18/06614-4, 14/25681-3)