Mechanisms of disease susceptibility and resistance in experimental Mayaro fever in mice

• Grant number: 18/03917-6
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2018 - June 30, 2020
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Rafael Elias Marques Pereira Silva
• Grantee: Rafael Elias Marques Pereira Silva
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Climate change is a worldwide reality that has facilitated the emergence of mosquito-borne viral diseases. Genus Alphavirus comprise dozens of mosquito-borne viruses that can cause severe disease in humans. However, most alphaviruses are neglected in terms of research and public policies. In the context of emergence, the lack of therapies and knowledge on neglected arboviral diseases impairs measures for disease control, prevention and treatment, resulting in dire consequences for affected populations. To address this problem, we propose the establishment of a panel of in vivo experimental models of disease caused by Mayaro virus (MAYV). MAYV is an emergent neglected arbovirus present in Brazil, whose infection lacks an specific treatment and vaccine. Our strategy consists in investigating mechanisms of disease pathogenesis involved in MAYV-induced articular disease, using mouse models of infection developed in susceptible (type I Interferon-deficient) and wild-type mice, to overcome inherent limitations of each mouse model. Moreover, we will combine gold-standard methodology in virology, immunology and pathology to a new microtomography technique developed in the host-institution to study local inflammation associated to MAYV infection. This project will result in a better understanding of MAYV biology and pathogenesis of MAYV-induced disease, and in the discovery and testing of potential treatments. Perspectives arising from this project include the study of MAYV structural biology and the correlation of our findings with related viral diseases. This project is based on the specialty of the proponent, who is experienced in the study of arboviral diseases such as Dengue, Yellow fever, St. Louis Encephalitis and Zika, in institutions in Brazil and abroad. This project will involve national and international research groups in active collaboration, and has already resulted in the establishment of a new field of research in the host-institution. (AU)

Scientific publications

(4)

(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)

ROCHA, REBECA FROES; DEL SARTO, JULIANA L.; GOMES, GIOVANNI F.; GONCALVES, MARIANA P.; RACHID, MILENE A.; SMETANA, JULIANA H. C.; SOUZA, DANIELE G.; TEIXEIRA, MAURO MARTINS; MARQUES, RAFAEL ELIAS. Type I interferons are essential while type II interferon is dispensable for protection against St. Louis encephalitis virus infection in the mouse brain. VIRULENCE, v. 12, n. 1, p. 244-259, JAN 1 2021. (18/03917-6, 18/10990-1)

RIBEIRO-FILHO, V, HELDER; COIMBRA, LAIS D.; CASSAGO, ALEXANDRE; ROCHA, REBECA P. F.; DA SILVA GUERRA, JOAO VICTOR; DE FELICIO, RAFAEL; CARNIELI, CAROLINA MORETTO; LEME, LUIZA; PADILHA, ANTONIO CLAUDIO; PAES LEME, ADRIANA F.; et al. Cryo-EM structure of the mature and infective Mayaro virus at 4.4 angstrom resolution reveals features of arthritogenic alphaviruses. NATURE COMMUNICATIONS, v. 12, n. 1, MAY 24 2021. (18/00629-0, 18/03917-6, 17/15340-2)

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)

DE CARVALHO, ANA CAROLINA; DIAS, CARLOS SATO B.; COIMBRA, LAIS D.; ROCHA, REBECA P. F.; BORIN, ALEXANDRE; FONTOURA, MARINA A.; CARVALHO, MURILO; PROOST, PAUL; NOGUEIRA, MAURICIO L.; CONSONNI, SILVIO R.; et al. Characterization of Systemic Disease Development and Paw Inflammation in a Susceptible Mouse Model of Mayaro Virus Infection and Validation Using X-ray Synchrotron Microtomography. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 5, p. 17-pg., 2023-03-01. (18/02594-9, 18/02993-0, 18/03917-6, 18/10990-1)