Vigilância genômica e análise transcriptômica na caracterização de doenças febris agudas: auxílio no monitoramento e manejo de epidemias no Brasil

Abstract

The Brazilian epidemiological scenario is characterized by the co-circulation of different arboviruses, including DENV and CHIKV, with greater prevalence. However, there are reports of the circulation of other neglected arboviruses, such as WNV, but with great potential for dissemination. In a country endemic for different arboviruses, patient management becomes even more complicated, given the high demand on health resources, the possibility of co-infection and prognoses for severity. Using a combined approach of viral surveillance and characterization of the host-pathogen response, the present work aims to characterize pathogens that cause acute febrile episodes with epidemic potential, as well as use Chikungunya virus infection as a model for characterizing the differential expression of transcripts associated with host immunological response in different prognoses. This study can, in addition to molecularly characterizing and describing the viral lineages related to outbreaks of Chikungunya and Dengue viruses in different regions of the country since 2017, provide an understanding of vulnerability to the entry of neglected emerging viral pathogens, such as WNV. Combined with surveillance, the data provided indications of possible dispersal routes, as well as helping to characterize susceptible populations and regions, thus guiding control and prevention measures. Based on the characterization of a new mutational pattern in the DENV-1 genotype V lineage and complex symptoms in individuals with chronic Chikungunya, this study reinforces the need to combine functional assays, aiming to characterize possible worsening of the disease and pathways associated with the persistence of these symptoms. Additionally, this study sheds light on the application of modern next-generation sequencing and public health techniques to expand understanding of the pathophysiology of the disease, optimize therapeutic options and reduce economic and quality of life damages for affected individuals.