Studies with Bunyaviridae that produce human disease

• Grant number: 14/02438-6
• Support type: Research Projects - Thematic Grants
• Duration: April 01, 2015 - March 31, 2019
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Luiz Tadeu Moraes Figueiredo
• Grantee: Luiz Tadeu Moraes Figueiredo
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto, SP, Brazil
• Co-Principal Investigators: Eurico de Arruda Neto ; Luis Lamberti Pinto da Silva
• Associated grant(s): 18/50016-4 - Experimental infection of neotropical bats with Hantavirus, AP.R
• Associated scholarship(s): 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; + associated scholarships 17/13981-0 - Characterization, genomics and diagnostic of viruses with importance for public health in Brazil by high throughput e 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)