RESUMEN
The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.
Asunto(s)
Artritis/inmunología , Fiebre Chikungunya/inmunología , Virus Chikungunya/fisiología , Citidina Desaminasa/inmunología , Proteínas/inmunología , Replicación Viral/inmunología , Adulto , Animales , Artritis/patología , Artritis/virología , Fiebre Chikungunya/patología , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Femenino , Fiebre/inmunología , Fiebre/patología , Fiebre/virología , Estudios de Seguimiento , Humanos , Interleucina-1beta/inmunología , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/inmunologíaRESUMEN
BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arbovirus that is causing outbreaks in several countries of the Americas. The virus was introduced in Brazil in 2014, and since then, several Brazilian states have notified autochthonous cases. OBJECTIVES: Provide additional evidence on a CHIKV outbreak and an outline of the laboratory and clinical profile of symptomatic patients in Sergipe, Brazil. STUDY DESIGN: In February 2016, we collected 142 serum samples from symptomatic patients for arboviruses in Sergipe, Brazil. All samples were submitted to qRT-PCR for the emerging arboviruses circulating in Brazil - ZIKV, CHIKV, and DENV - and later submitted to the immunoenzymatic assay. RNA positive samples were randomly selected and sequenced for characterization of the genotype involved in the outbreak. RESULTS: Our study had 75.35% (107/142) positivity for CHIKV infection, with all age groups and genera being equally infected. The virus was identified in 11 of the 13 cities studied in that state, including the ECSA genotype. Importantly, fever was the only statistically significant symptoms for CHIKV infection (p<0.05), while asthenia was significantly associated with symptomatic patients that were CHIKV-negative (p<0.05). CONCLUSIONS: Our findings support the importance of fever as a clinical marker and contribute to molecular and serological surveillance data, which may help in the understanding of CHIKV circulation, emergence and clinical description.
Asunto(s)
Fiebre Chikungunya/epidemiología , Virus Chikungunya/genética , Virus Chikungunya/inmunología , Brotes de Enfermedades , Vigilancia de la Población , Poblaciones Vulnerables , Adolescente , Adulto , Brasil/epidemiología , Fiebre Chikungunya/sangre , Fiebre Chikungunya/inmunología , Fiebre Chikungunya/virología , Virus Chikungunya/clasificación , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Femenino , Fiebre/epidemiología , Fiebre/etiología , Genotipo , Humanos , Técnicas para Inmunoenzimas , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Filogenia , ARN Viral/sangre , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
BACKGROUND: The worldwide expansion of new emergent arboviruses such as Chikungunya and Zika reinforces the importance in understanding the role of mosquito species in spreading these pathogens in affected regions. This knowledge is essential for developing effective programs based on species specificity to avoid the establishment of endemic transmission cycles sustained by the identified local vectors. Although the first autochthonous transmission of Chikungunya virus was described in 2014 in the north of Brazil, the main outbreaks were reported in 2015 and 2016 in the northeast of Brazil. METHODOLOGY/PRINCIPAL FINDINGS: During 5 days of February 2016, we collected mosquitoes in homes of 6 neighborhoods of Aracaju city, the capital of Sergipe state. Four mosquito species were identified but Culex quinquefasciatus and Aedes aegypti were the most abundant. Field-caught mosquitoes were tested for Chikungunya (CHIKV), Zika (ZIKV) and Dengue viruses (DENV) by qRT-PCR and one CHIKV-infected Ae. aegypti female was detected. The complete sequence of CHIKV genome was obtained from this sample and phylogenetic analysis revealed that this isolate belongs to the East-Central-South-African (ECSA) genotype. CONCLUSIONS: Our study describes the first identification of a naturally CHIKV-infected Ae. aegypti in Brazil and the first report of a CHIKV from ECSA genotype identified in this species in the Americas. These findings support the notion of Ae. aegypti being a vector involved in CHIKV outbreaks in northeast of Brazil.