Desenvolvimento de modelos experimentais em C57BL/6 para estudos de coinfecção com o vírus Mayaro e Chikungunya
Data
2023-12-01
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Trabalho de conclusão de curso
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As mudanças climáticas, ambientais e ecológicas levaram ao aumento recente dos surtos epidêmicos de arboviroses no Brasil, dentre eles o Chikungunya (CHIKV) e o Mayaro (MAYV). Ambos CHIKV e MAYV são membros da família Togaviridae, gênero Alphavirus, do complexo antigênico Semliki Forest e filogeneticamente próximos. Enquanto o CHIKV é o agente causador de surtos no mundo todo, a infecção pelo MAYV representa um problema crescente de saúde pública na América Latina, com casos esporádicos e surtos geograficamente limitados. No entanto, o MAYV permanece extremamente negligenciado, com número de casos ainda subestimado, devido a similaridade dos sintomas clínicos com chikungunya e dengue. Estudos recentes mostraram que a exposição prévia à um alphavírus, desencadeia em indivíduos expostos uma potente resposta humoral capaz de conferir tanto uma proteção contra uma reinfecção, como uma proteção parcial cruzada contra uma reinfecção heteróloga. Dessa forma, esse projeto tem como objetivo estabelecer diferentes modelos de coinfecção com o CHIKV e MAYV em camundongos C57BL/6 adultos imunologicamente competentes, para estudar de que forma essa coinfecção modula a resposta imune humoral mediada por anticorpos e como ela pode alterar o curso da infecção de ambos os vírus. Para isso, será realizada a quantificação da viremia, avaliação dos sinais clínicos da doença, detecção de anticorpos séricos e análise histopatológica.
Climatic, environmental and ecological changes have led to the recent increase in epidemic outbreaks of arboviruses in Brazil, including Chikungunya (CHIKV) and Mayaro (MAYV). Both CHIKV and MAYV are members of the family Togaviridae, genus Alphavirus, of the Semliki Forest antigenic complex, and phylogenetically related. While CHIKV is the causative agent of outbreaks worldwide, MAYV infection represents a growing public health problem in Latin America, with sporadic cases and outbreaks. However, MAYV remains extremely neglected, with the number of cases still underestimated, due to the similarity of clinical symptoms with chikungunya and dengue. Recent studies have shown that previous exposure to an alphavirus triggers a potent humoral response in exposed individuals capable of conferring both protection against reinfection and partial cross-protection against heterologous reinfection. Thus, this project aims to establish different models of co-infection with CHIKV and MAYV in immunologically competent adult C57BL/6 mice, to study how this coinfection modulates the antibody-mediated humoral immune response and how it can alter the course of infection of both viruses. For this, the quantification of viremia, evaluation of the clinical signs of the disease, detection of serum antibodies and histopathological analysis will be performed.
Climatic, environmental and ecological changes have led to the recent increase in epidemic outbreaks of arboviruses in Brazil, including Chikungunya (CHIKV) and Mayaro (MAYV). Both CHIKV and MAYV are members of the family Togaviridae, genus Alphavirus, of the Semliki Forest antigenic complex, and phylogenetically related. While CHIKV is the causative agent of outbreaks worldwide, MAYV infection represents a growing public health problem in Latin America, with sporadic cases and outbreaks. However, MAYV remains extremely neglected, with the number of cases still underestimated, due to the similarity of clinical symptoms with chikungunya and dengue. Recent studies have shown that previous exposure to an alphavirus triggers a potent humoral response in exposed individuals capable of conferring both protection against reinfection and partial cross-protection against heterologous reinfection. Thus, this project aims to establish different models of co-infection with CHIKV and MAYV in immunologically competent adult C57BL/6 mice, to study how this coinfection modulates the antibody-mediated humoral immune response and how it can alter the course of infection of both viruses. For this, the quantification of viremia, evaluation of the clinical signs of the disease, detection of serum antibodies and histopathological analysis will be performed.
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Trabalho de Conclusão de Curso