Study of emerging Alphuvirus infections in cell lines of the genus Aedes and their influence on the apoptosis pathway

• Grant number: 24/21199-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Carla Torres Braconi
• Grantee: Lucas Paiato Margato
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Arboviruses, transmitted by arthropods, form a non-taxonomic group composed mainly of viruses with an RNA genome. These viruses significantly impact the emergence and spread of viral diseases in tropical and subtropical regions. These viruses directly affect the health of humans and other mammals and profoundly influence public health strategies and understanding of global ecology. Most infections are asymptomatic, but individuals who develop symptoms may develop fever, myalgia, rashes, arthralgia, and, in a smaller proportion, cases lead to death. Within this group of viruses, the genus Alphavirus is part of the small family Togaviridae, which includes around 30 viral species considered critical to human health. These viruses are transmitted to human hosts through the bites of hematofagous mosquitoes. Interestingly, mosquito vectors have developed mechanisms to tolerate persistent infections and rely on efficient antiviral strategies to restrict viral replication to nonpathogenic levels.Two examples of the Alphavirus genus, Chikungunya virus (CHIKV) and Mayaro virus (MAYV), cause human infections in the Americas. Recently, CHIKV expanded its geographic distribution (2004-2014), and the Mayaro virus (MAYV), associated with sporadic outbreaks mainly in Central and South America. The Mayaro virus has not yet effectively implemented an urban cycle in Brazil. Therefore, this project aims to understand the infection pattern of these two viruses in insect cells that spread arboviruses in Brazil: A. albopictus and A. aegypti, using immortalized cell lines, C6/36 (ATCC CRL-1660) as models. and Aag2 (ATCC CCL-125). In these models, the context of viral infection with CHIKV and MAYV, in this project we will investigate intra and extracellular viral load, and the influence of this infection on the expression of genes related to cell apoptosis. For this, the methodology will include the construction of viral load standard curves, viral infection kinetics assays in cell lines and evaluation of the expression of viral and cellular genes of the apoptosis pathway in the same cell lines.