RESUMO
Dengue virus (DENV) transmission to human populations requires infection of vector mosquitoes as an essential component of the transmission process. DENV transmission leads to infections that range from asymptomatic to life-threatening pathologies, such as dengue hemorrhagic fever and dengue shock syndrome. Aedes aegypti is the principal vector of DENV, and its vector competence consists of the intrinsic factors, genes, molecules, and pathways that allow infection, replication, and dissemination of this virus throughout the cells of mosquito tissues. In the search for mosquito molecular targets to block DENV transmission, the effect of DENV infection on mosquitoes has been an important focus of research. In this study, we review the findings of research on the effect of DENV infection on mosquito tissue cells and the immunity pathways and molecules that are involved in this infection. We emphasize the relevance of recent findings to understand the relationship between Ae. aegypti immune response, vector competence, and DENV transmission to human hosts.
Assuntos
Aedes/imunologia , Aedes/virologia , Dengue/transmissão , Animais , Dengue/virologia , Humanos , Imunidade , Mosquitos Vetores/imunologia , Mosquitos Vetores/virologiaRESUMO
OBJECTIVE: To identify and characterize Aedes aegypti's AAEL006536 gene proximal upstream cis-regulatory sequences activated by dengue virus infection. MATERIALS AND METHODS: A. aegypti Rockefeller strain mosquitoes were blood fed or infected with dengue virus 2. Open chromatinprofiling was then carried out in pools of midguts from each group of mosquitoes. RESULTS: The proximal upstream region does not contain open chromatin sites in the midguts of blood-fed mosquitoes as detected by FAIRE-qPCR. In contrast, two cis-regulatory sites were identified in the same upstream region of dengue virus-infected mosquito midguts. The distal sequence contains STAT-, REL- and C/EBP-type transcription factor binding sites. CONCLUSIONS: The activation of two proximal cis-regulatory sequences, induced by dengue virus infection, is mediated by chromatin remodeling mechanisms. Binding sites suggest a dengue virus infectioninduced participation of immunity transcription factors in the up-regulation of this gene. This suggests the participation of the AAEL006536 gene in the mosquito's antiviral innate immune response.
Assuntos
Aedes/genética , Vírus da Dengue/fisiologia , Genes de Insetos , Proteínas de Insetos/genética , Mosquitos Vetores/genética , Aedes/imunologia , Animais , Montagem e Desmontagem da Cromatina , Feminino , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno , Imunidade Inata , Intestinos/virologia , Mosquitos Vetores/imunologia , Análise de Sequência de DNARESUMO
Abstract: Objective: To identify and characterize Aedes aegypti's AAEL006536 gene proximal upstream cis-regulatory sequences activated by dengue virus infection. Materials and methods: A. aegypti Rockefeller strain mosquitoes were blood fed or infected with dengue virus 2. Open chromatin profiling was then carried out in pools of midguts from each group of mosquitoes. Results: The proximal upstream region does not contain open chromatin sites in the midguts of blood-fed mosquitoes as detected by FAIRE-qPCR. In contrast, two cis-regulatory sites were identified in the same upstream region of dengue virus-infected mosquito midguts. The distal sequence contains STAT-, REL- and C/EBP-type transcription factor binding sites. Conclusion: The activation of two proximal cis-regulatory sequences, induced by dengue virus infection, is mediated by chromatin remodeling mechanisms. Binding sites suggest a dengue virus infection-induced participation of immunity transcription factors in the up-regulation of this gene. This suggests the participation of the AAEL006536 gene in the mosquito's antiviral innate immune response.
Resumen: Objetivo: Identificar y caracterizar las secuencias reguladoras activadas por la infección por virus dengue en la región proximal del gen AAEL006536 de Aedes aegypti. Material y métodos: Mosquitos de la cepa Rockefeller de A. aegypti se infectaron con virus dengue o se alimentaron con sangre. Se obtuvieron los perfiles de cromatina abierta del locus en los intestinos de cada uno de los grupos. Resultados: Se identificaron dos sitios reguladores solo en los intestinos de mosquitos infectados por virus dengue. El sitio distal contiene sitios de unión a factores de transcripción tipo REL, STAT y C/EBP. Conclusiones: La activación de dos sitios reguladores proximales está mediada por la remodelación de la cromatina. Los sitios de unión a factores de transcripción en el sitio regulador distal sugieren la participación de las vías de inmunidad en la regulación del gen. Esto sugiere la participación de este gen en la respuesta inmune del mosquito frente a la infección viral.
Assuntos
Animais , Feminino , Genes de Insetos , Proteínas de Insetos/genética , Aedes/genética , Vírus da Dengue/fisiologia , Mosquitos Vetores/genética , Regulação Viral da Expressão Gênica , Análise de Sequência de DNA , Aedes/imunologia , Montagem e Desmontagem da Cromatina , Interações Hospedeiro-Patógeno , Mosquitos Vetores/imunologia , Imunidade Inata , Intestinos/virologiaRESUMO
The innate immune response of Anopheles gambiae involves the transcriptional upregulation of effector genes. Therefore, the cis-regulatory sequences and their cognate binding factors play essential roles in the mosquito's immune response. However, the genetic control of the mosquito's innate immune response is not yet fully understood. To gain further insight on the elements, the factors and the potential mechanisms involved, an open chromatin profiling was carried out on A. gambiae-derived immune-responsive cells. Here, we report the identification of cis-regulatory sites, immunity-related transcription factor binding sites, and cis-regulatory modules. A de novo motif discovery carried out on this set of cis-regulatory sequences identified immunity-related motifs and cis-regulatory modules. These modules contain motifs that are similar to binding sites for REL-, STAT-, lola- and Deaf1-type transcription factors. Sequence motifs similar to the binding sites for GAGA were found within a cis-regulatory module, together with immunity-related transcription factor binding sites. The presence of Deaf1- and lola-type binding sites, along with REL- and STAT-type binding sites, suggests that the immunity function of these two factors could have been conserved both in Drosophila and Anopheles gambiae.
