Emerging and re-emerging viruses: biology, pathogenesis and prospection

• Grant number: 19/26119-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2021
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Eurico de Arruda Neto
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais:( Atuais ): Benedito Antônio Lopes da Fonseca ; Luiz Tadeu Moraes Figueiredo
• Pesquisadores principais:( Anteriores ): Luis Lamberti Pinto da Silva
• Associated researchers: Fernando Chahud ; Luis Lamberti Pinto da Silva ; Osvaldo Massaiti Takayanagui ; Wilma Terezinha Anselmo Lima
• Associated research grant(s): 24/02163-9 - Study of the mechanisms of assembly and budding of the arboviruses Oropouche and Zika in neurons and the effects of infection on neuronal proteostasis, AP.R; 23/01587-7 - Experimental maternal viral infections and responses of offsprings to the challenge: repercussions on protection and susceptibility, AP.R; 22/15883-4 - Multiuser equipment awarded in the process 2019/26119-0: QuantiStudio 5 Real-Time PCR System, AP.EMU; 22/15881-1 - Multi-user equipement awarded as part of process 2019/26119-0: plate multimode reader Varioskan LUX, AP.EMU
• Associated scholarship(s): 24/06237-7 - Impact of Pandemic Respiratory Viruses Influenza A and SARS-CoV-2 on Mitochondrial Function in Lymphoid Tissues, BP.PD; 24/21434-3 - Processing of human lymphoid tissues to obtain primary cultures and detect coronaviruses and influenza viruses, BP.TT; 24/10555-4 - Oropouche virus pathogenesis: Functions of non-structural proteins of the medium (NSm) and small segments (NSs)., BP.MS; + associated scholarships 24/05889-0 - Influenza A virus persistence in experimentally infected mouse tissues: the role of Il-10, BP.MS; 24/17560-3 - Processing of human lymphoid tissues for culture and testing of respiratory viruses by real-time PCR., BP.TT; 24/05890-9 - Experimental respiratory syncytial virus infection during pregnancy: maternal-fetal susceptibility and protection via lactation., BP.MS; 24/16105-0 - Study of the influence of Oropouche virus infection on the intracellular trafficking of amyloid precursor protein (APP) in mouse neurons., BP.IC; 24/04121-1 - In vitro inflamassome activation by SARS-CoV-2 variants in infected monocytes and macrophages., BP.IC; 24/05524-2 - Evaluation of the influence of the osteopontin protein in modulating the cellular inflammatory response after in vitro infection by Chikungunya virus and its therapeutic potential, BP.PD; 23/12540-1 - Generation of knockout cell lines for effector proteins of the endomembrane system, BP.TT; 23/05503-2 - Analysis of the CREB3 regulatory factor importance on the replication of Zika virus in trophoblasts., BP.IC; 23/02880-0 - Study of the interactions between SARS-CoV2 and the host cell endomembrane system., BP.PD; 22/15243-5 - Study of ex vivo infection of human secondary lymphoid tissue with pandemic viruses: Influenza and SARS-CoV-2., BP.MS; 22/15799-3 - Genomics of viruses associated with human disease., BP.PD; 22/10751-2 - SARS-CoV-2 Spleen Infection Study, BP.IC; 22/12726-5 - Generation of cell lines knockout for vesicle coat adapters (APs)., BP.TT; 22/08111-5 - Analysis of single-cell gene expression of human lymphoid tissues infected by pandemic respiratory viruses: SARS-CoV-2 and Influenza, BP.PD; 22/04533-2 - Study of Oropouche virus trafficking and its relationship with the autophagic pathway modulation during host cell infection, BP.MS; 22/09032-1 - Processing of human lymphoid tissues to obtain primary cultures and detect coronavirus and Influenza virus., BP.TT; 22/01255-1 - Sample processing of neotropicals non-human primates and small mammals and coronavirus detection through RT-PCR and/or RT-qPCR, BP.TT; 22/01222-6 - Role of OROV non-structural proteins in its pathogenesis, BP.IC; 21/05869-1 - Influenza virus infection of TCD8+ lymphocytes, BP.MS; 21/13940-8 - Processing human lymphoid tissues to obtain primary cultures and detect coronavirus and influenza virus, BP.TT - associated scholarships

Abstract

This thematic research project is proposed based on a central backbone of research on viruses of great importance for human health. The proposal comes from five collaborative research groups, led by established professors, and consists of subprojects distributed in four major areas of work: 1) Virus-cell interaction; 2) Pathogenesis of viral infections; 3) Diagnosis and prospection of human viruses; 4) Testing of drugs and antiviral vaccines. The pathogens to be addressed in this Thematic are: the human immunodeficiency virus (HIV); Zika arboviruses (ZIKV), Oropouche (OROV), Mayaro (MAYV), Chikungunya (CHIKV), Dengue (DENV), West Nile (WNV), Yellow Fever (YFV), Saint Louis Encephalitis (SLEV), and Rocio (ROCV); hantaviruses causing pulmonary and cardiovascular syndrome; arenavirus; and the respiratory viruses influenza A (IAV), respiratory syncytial (RSV), metapneumovirus (MPV), rhinovirus (RV), and enterovirus (EV). The great importance of these agents for human health is reflected in the substantial spread of zoonotic viruses in Brazil, causing diseases including congenital syndromes; in the 38 million people living with HIV in the world, and in the high frequencies of respiratory viral infections, the most frequent infections of humankind. In addition to these specific viruses, viromes of human tissues and blood samples will be prospected, as well as of zoonotic viruses as potentials threats to human health. Viruses will be investigated in various experimental models, including studies on entry, assembly, intracellular traffic, and externalization of viruses in exosomes; modes of viral antagonism and modulation of host antiviral factors; viral effects on proteostasis in neurons; viral effects on endoplasmic reticulum stress, autophagy and inflammasome; modulation of cellular inflammatory response in arbovirus infection; cell biology of virus persistence in lymphohematopoietic tissues; arbovirus pathogenesis; cell biology of virus infection in bat cells; humoral response to flaviviruses and their cross-reactions; single-cell analysis of functional genomics of viruses; placental infection and vertical virus transmission; development of broad-spectrum diagnosis of acute febrile and CNS diseases by massive sequencing in MinION and by DNA and peptide microarrays; prospection and eco-epidemiology of zoonotic viruses; viromes of patients with acute febrile illness; arbovirus detection in avian fauna; and development of antiviral drugs and vaccines. The scientific challenges are clear, and we are convinced that we can tackle them on the basis of well-planned strategies, with collaborations between teams, including technicians, postdocs, postgraduate and undergraduate students. In addition, the Virology Research Center, created at USP Ribeirão Preto thanks to FAPESP, has a well equiped structure, with BSL2 and BSL3 laboratories, an experimental vivarium, and a solid support network in the institution's multiuser facilities. This project has the potential to make important discoveries in virology, some of fundamental nature, that could expand knowledge and even serve as a basis for developing products. (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)

FUMAGALLI, MARCILIO JORGE; MORAES FIGUEIREDO, LUIZ TADEU; AQUINO, VICTOR HUGO. Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, AUG 12 2021. (19/26119-0, 18/09383-3, 19/27333-6)

FUMAGALLI, MARCILIO JORGE; CASTRO-JORGE, LUIZA ANTUNES; DE SOUZA, WILLIAM MARCIEL; DE AZEVEDO, PATRICK ORESTES; HANSEN, ALANA WITT; GAZZINELLI, RICARDO TOSTES; DA FONSECA, BENEDITO ANTONIO LOPES; SPILKI, FERNANDO ROSADO; FIGUEIREDO, LUIZ TADEU MORAES. oronaVac and ChAdOx1 Vaccination and Gamma Infection Elicited Neutralizing Antibodies against the SARS-CoV-2 Delta Varian. IRUSES-BASE, v. 14, n. 2, FEB 2022. (18/09383-3, 20/05527-0, 19/26119-0)

FUMAGALLI, MARCILIO JORGE; CAPATO, CARLOS FABIANO; DE CASTRO-JORGE, LUIZA ANTUNES; DE SOUZA, WILLIAM MARCIEL; ARRUDA, EURICO; FIGUEIREDO, LUIZ TADEU MORAES. Stability of SARS-CoV-2 and other airborne viruses under different stress conditions. ARCHIVES OF VIROLOGY, v. 167, n. 1, NOV 2021. (18/09383-3, 19/26119-0, 19/27333-6)

ALMEIDA, GLAUCIA M.; SILVA, BRUNA M.; ARRUDA, EURICO; SEBOLLELA, ADRIANO. Human brain tissue cultures: a unique ex vivo model to unravel the pathogenesis of neurotropic arboviruses. CURRENT OPINION IN VIROLOGY, v. 70, p. 8-pg., 2025-02-01. (21/10925-8, 19/26119-0, 21/12263-2)

ALVIM, JONAS C.; BOLT, ROBERT M.; AN, JING; KAMISUGI, YASUKO; CUMING, ANDREW; SILVA-ALVIM, FERNANDA A. L.; CONCHA, JUAN O.; DA SILVA, LUIS L. P.; HU, MEIYI; HIRSZ, DOMINIQUE; et al. The K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper. NATURE COMMUNICATIONS, v. 14, n. 1, p. 16-pg., 2023-03-23. (20/11900-6, 19/26119-0, 19/02418-9)

FUMAGALLI, MARCILIO JORGE; CASTRO-JORGE, LUIZA ANTUNES; FRAGA-SILVA, THAIS FERNANDA DE CAMPOS; DE AZEVEDO, PATRICK ORESTES; CAPATO, CARLOS FABIANO; RATTIS, BRUNA AMANDA CRUZ; HOJO-SOUZA, NATALIA SATCHIKO; FLORIANO, VITOR GONCALVES; DE CASTRO, JULIA TEIXEIRA; RAMOS, SIMONE GUSMAO; et al. Protective Immunity against Gamma and Zeta Variants after Inactivated SARS-CoV-2 Virus Immunization. Viruses-Basel, v. 13, n. 12, DEC 2021. (19/26119-0, 20/05527-0, 18/09383-3, 19/09881-6, 19/11213-1)

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)

SOUZA, JULIANO DE PAULA; DE JESUS, BRUNA LAIS SANTOS; GIUSTI, ANDRE LUIZ; VIANA, ROSA MARIA MENDES; CARDOSO, RICARDO DE SOUZA; ALMEIDA, GLAUCIA MARIA; PONTELLI, MARJORIE CORNEJO; KUMMERER, BEATE MAREIKE; ESPOSITO, DANILLO LUCAS ALVES; DE MELO, DANILO MACHADO; et al. Breastfeeding by chikungunya virus-infected dams confers resistance to challenge in the offspring. TRANSLATIONAL RESEARCH, v. 255, p. 10-pg., 2023-04-04. (14/02438-6, 19/26119-0)

DE LIMA, THAIS MELQUIADES; MARTINS, RONALDO BRAGANCA; MIURA, CAROLINA SPONCHIADO; OLIVEIRA SOUZA, MARIA VITORIA; ANZOLINI CASSIANO, MURILO HENRIQUE; RODRIGUES, TAMARA SILVA; VERAS, FLAVIO PROTASIO; SOUSA, JOSANE DE FREITAS; GOMES, ROGERIO; DE ALMEIDA, GLAUCIA MARIA; et al. Tonsils are major sites of persistence of SARS-CoV-2 in children. MICROBIOLOGY SPECTRUM, v. 11, n. 5, p. 14-pg., 2023-10-01. (19/26119-0, 20/07063-1)

CONCHA, JUAN O.; GUTIERREZ, KRISTEL; BARBOSA, NATALIA; RODRIGUES, ROGER L.; DE CARVALHO, ANDREIA N.; TAVARES, LUCAS A.; RUDD, JARED S.; COSTA, CRISTINA S.; ANDRADE, BARBARA Y. G.; ESPREAFICO, ENILZA M.; et al. Rab27a GTPase and its effector Myosin Va are host factors required for efficient Oropouche virus cell egress. PLOS PATHOGENS, v. 20, n. 8, p. 24-pg., 2024-08-01. (19/26119-0, 19/02945-9, 23/02880-0, 22/04533-2, 20/11900-6, 21/01182-1, 16/18356-4, 18/00297-7, 19/27725-1, 19/02418-9)