Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 664
Filtrar
1.
Nat Commun ; 12(1): 5374, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508072

RESUMO

The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision-guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate flightless females and sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and even eliminate mosquito populations. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.


Assuntos
Aedes/virologia , Infertilidade Masculina/veterinária , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Aedes/genética , Animais , Animais Geneticamente Modificados , Arbovírus , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Feminino , Humanos , Infertilidade Masculina/genética , Masculino , Modelos Biológicos , Mosquitos Vetores/genética , Febre Amarela/prevenção & controle , Febre Amarela/transmissão , Febre Amarela/virologia , Zika virus , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
2.
Arch Virol ; 166(10): 2895-2899, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34351521

RESUMO

After the 2005-2009 chikungunya epidemic, intermittent outbreaks were reported in many parts of India. The outbreaks were caused by either locally circulating strains or imported viruses. Virus transmission routes can be traced by complete genome sequencing studies. We investigated two outbreaks in 2014 and 2019 in Kerala, India. Chikungunya virus (CHIKV) was isolated from the samples, and whole genomes were sequenced for a 2014 isolate and a 2019 isolate. Phylogenetic analysis revealed that the isolates formed a separate group with a 2019 isolate from Pune, Maharashtra, and belonged to the East/Central/South African (ECSA) genotype, Indian subcontinent sublineage of the Indian Ocean Lineage (IOL). A novel mutation at amino acid position 76 of the E2 gene was observed in the group. The phylogenetic results suggest that the outbreaks might have been caused by a virus that had been circulating in India since 2014. A detailed study is needed to investigate the evolution of CHIKV in India.


Assuntos
Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Surtos de Doenças , Febre de Chikungunya/transmissão , Vírus Chikungunya/classificação , Vírus Chikungunya/isolamento & purificação , Genoma Viral/genética , Genótipo , Humanos , Índia/epidemiologia , Mutação , Filogenia , RNA Viral/genética , Proteínas do Envelope Viral/genética
3.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360656

RESUMO

Chikungunya virus (CHIKV) is a mosquito-transmitted infectious agent that causes an endemic or epidemic outbreak(s) of Chikungunya fever that is reported in almost all countries. This virus is an intense global threat, due to its high rate of contagion and the lack of effective remedies. In this study, we developed two baculovirus expression vector system (BEVS)-based approaches for the screening of anti-CHIKV drugs in Spodoptera frugiperda insect (Sf21) cells and U-2OS cells. First, structural protein of CHIKV was co-expressed through BEVS and thereby induced cell fusion in Sf21 cells. We used an internal ribosome entry site (IRES) to co-express the green fluorescent protein (EGFP) for identifying these fusion events. The EGFP-positive Sf21 cells fused with each other and with uninfected cells to form syncytia. We identified that ursolic acid has potential anti-CHIKV activity in vitro, by using this approach. Second, BacMam virus-based gene delivery has been successfully applied for the transient expression of non-structural proteins with a subgenomic promoter-EGFP (SP-EGFP) cassette in U-2OS cells to act as an in vitro CHIKV replicon system. Our BacMam-based screening system has identified that the potential effects of baicalin and baicalein phytocompounds can inhibit the replicon activity of CHIKV in U-2OS cells. In conclusion, our results suggested that BEVS can be a potential tool for screening drugs against CHIKV.


Assuntos
Antivirais/farmacologia , Baculoviridae/genética , Fusão Celular , Febre de Chikungunya/tratamento farmacológico , Vírus Chikungunya/efeitos dos fármacos , Proteínas do Envelope Viral/metabolismo , Replicação Viral , Animais , Febre de Chikungunya/virologia , Vetores Genéticos/genética , Proteínas de Fluorescência Verde , Ensaios de Triagem em Larga Escala , Mosquitos Vetores , Células Sf9 , Proteínas do Envelope Viral/genética
4.
Nat Commun ; 12(1): 4636, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330906

RESUMO

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/classificação , Vírus Chikungunya/fisiologia , Citocinas/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Fadiga/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunoglobulina G/imunologia , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinação/métodos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
5.
BMC Infect Dis ; 21(1): 639, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215212

RESUMO

BACKGROUND: Infection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated. Cytokines, which broadly also include chemokines and growth factors, have been shown to play a role in protective immunity as well as DENV and CHIKV pathogenesis. However, differences in cytokine response to both viruses remain poorly understood, especially in patients from countries where both viruses are endemic. Our study is therefore aimed to provide a comparative profiling of cytokine response induced by acute DENV and CHIKV infections in patients with similar disease stages and in experimental in vitro infections. METHODS: By using multiplex immunoassay, we compared host cytokine profiles between acute CHIKV and DENV infections by analysing serum cytokine levels of IL-1α, IL-4, IL-5, IL-8, IL-13, RANTES, MCP-3, eotaxin, PDGF-AB/BB, and FGF-2 from the sera of acute chikungunya and dengue fever patients. We further investigated the cytokine profile responses using experimental in vitro CHIKV and DENV infections of peripheral blood mononuclear cells (PBMCs). RESULTS: We found that both CHIKV and DENV-infected patients had an upregulated level of IL-8 and IL-4, with the highest IL-4 level observed in DENV-2 infected patients. Higher IL-8 level was also correlated with lower platelet count in dengue patients. IL-13 and MCP-3 downregulation was observed only in chikungunya patients, while conversely PDGF-AB/BB and FGF-2 downregulation was unique in dengue patients. Age-associated differential expression of IL-13, MCP-3, and IL-5 was also observed, while distinct kinetics of IL-4, IL-8, and FGF-2 expression between CHIKV and DENV-infected patients were identified. Furthermore, the unique pattern of IL-8, IL-13 and MCP-3, but not IL-4 expression was also recapitulated using experimental in vitro infection in PBMCs. CONCLUSIONS: Taken together, our study identified common cytokine response profile characterized by upregulation of IL-8 and IL-4 between CHIKV and DENV infection. Downregulation of IL-13 and MCP-3 was identified as a unique cytokine response profile of acute CHIKV infection, while distinct downregulation of PDGF-AB/BB and FGF-2 characterized the response from acute DENV infection. Our study provides an important overview of the host cytokine responses between CHIKV and DENV infection, which is important to further understand the mechanism and pathology of these diseases.


Assuntos
Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Citocinas/metabolismo , Vírus da Dengue/imunologia , Dengue/imunologia , Adolescente , Adulto , Idoso , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/metabolismo , Febre de Chikungunya/virologia , Criança , Pré-Escolar , Estudos Transversais , Citocinas/imunologia , Dengue/epidemiologia , Dengue/metabolismo , Dengue/virologia , Feminino , Humanos , Indonésia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
6.
PLoS Negl Trop Dis ; 15(6): e0009468, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34181663

RESUMO

BACKGROUND: Chikungunya fever (CHIKF) is a serious public health problem with a high rate of infection and chronic disabling manifestations that has affected more than 2 million people worldwide since 2005. In spite of this, epidemiological data on vulnerable groups such as Indigenous people are scarce, making it difficult to implement public policies in order to prevent this disease and assist these populations. OBJECTIVE: To describe the serological and epidemiological profile of chikungunya virus (CHIKV) in two Indigenous populations in Northeast Brazil, as well as in an urbanized control community, and to explore associations between CHIKV and anthropometric variables in these populations. METHODOLOGY/PRINCIPAL FINDINGS: This is a cross-sectional ancillary study of the Project of Atherosclerosis among Indigenous Populations (PAI) that included people 30 to 70 years old, recruited from two Indigenous tribes (the less urbanized Fulni-ô and the more urbanized Truká people) and an urbanized non-Indigenous control group from the same area. Subjects underwent clinical evaluation and were tested for anti-CHIKV IgG by enzyme-linked immunosorbent assay. Serological profile was described according to ethnicity, sex, and age. The study population included 433 individuals distributed as follows: 109 (25·2%) Truká, 272 (62·8%) Fulni-ô, and 52 (12%) from the non-Indigenous urbanized control group. Overall prevalence of CHIKV IgG in the study sample was 49.9% (216; 95% CI: 45·1-54·7). When the sample was stratified, positive CHIKV IgG was distributed as follows: no individuals in the Truká group, 78·3% (213/272; 95% CI: 72·9-83·1) in the Fulni-ô group, and 5.8% (3/52; 95% CI: 1.21-16) in the control group. CONCLUSIONS/SIGNIFICANCE: Positive tests for CHIKV showed a very high prevalence in a traditional Indigenous population, in contrast to the absence of anti-CHIKV serology in the Truká people, who are more urbanized with respect to physical landscape, socio-cultural, and historical aspects, as well as a low prevalence in the non-Indigenous control group, although all groups are located in the same area.


Assuntos
Anticorpos Antivirais/sangue , Febre de Chikungunya/sangue , Febre de Chikungunya/etnologia , Vírus Chikungunya/imunologia , Adulto , Idoso , Brasil/epidemiologia , Brasil/etnologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/sangue , Povos Indígenas/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
7.
Sci Rep ; 11(1): 12321, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112897

RESUMO

Reverse genetics is an important tool in the elucidation of viral replication and the development of countermeasures; however, these methods are impeded by laborious and inefficient replicon delivery methods. This paper demonstrates the use of a baculovirus to facilitate the efficient delivery of autonomous CHIKV replicons into mosquito and mammalian cells in vitro as well as adult mosquitoes in vivo. The efficacy of this approach was verified via co-localization among an eGFP reporter, nsP1, and dsRNA as well as through the inhibition of an RNA-dependent RNA polymerase (RdRp) null mutation (DDAA) in nsP4, or the treatment of a known antiviral compound (6-azauridine). We also investigated the correlation between CHIKV replicon-launched eGFP expression and the effectiveness of CHIKV replicon variants in inducing IFN-ß expression in human cell lines. This delivery method based on a single vector is applicable to mosquito and mammalian cells in seeking to decipher the mechanisms underlying CHIKV replication, elucidate virus-host interactions, and develop antivirals. This study presents an effective alternative to overcome many of the technological issues related to the study and utilization of autonomous arbovirus replicons.


Assuntos
Febre de Chikungunya/genética , Vírus Chikungunya/genética , RNA Polimerase Dependente de RNA/genética , Replicação Viral/genética , Aedes/virologia , Animais , Antivirais/farmacologia , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Chlorocebus aethiops/virologia , Culicidae/virologia , Humanos , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , RNA Viral/genética , Células Vero , Proteínas não Estruturais Virais/genética
8.
Viruses ; 13(6)2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063936

RESUMO

Baby hamster kidney-21 (BHK-21) cells are widely used to propagate and study many animal viruses using infection and transfection techniques. Among various BHK-21 cell clones, the fibroblast-like BHK-21/C-13 line and the epithelial-like BHK-21/WI-2 line are commonly used cell clones for alphavirus research. Here we report that BHK-21/WI-2 cells were significantly less susceptible to primary infection by the alphavirus chikungunya virus (CHIKV) than were BHK-21/C-13 cells. The electroporation efficiency of alphavirus RNA into BHK-21/WI-2 was also lower than that of BHK-21/C-13. The growth of CHIKV was decreased in BHK-21/WI-2 compared to BHK-21/C-13, while primary infection and growth of the alphavirus Sindbis virus (SINV) were equivalent in the two cell lines. Our results suggested that CHIKV entry could be compromised in BHK-21/WI-2. Indeed, we found that the mRNA level of the CHIKV receptor MXRA8 in BHK-21/WI-2 cells was much lower than that in BHK-21/C-13 cells, and exogenous expression of either human MXRA8 or hamster MXRA8 rescued CHIKV infection. Our results affirm the importance of the MXRA8 receptor for CHIKV infection, and document differences in its expression in two clonal cell lines derived from the original BHK-21 cell cultures. Our results also indicate that CHIKV propagation and entry studies in BHK-21 cells will be significantly more efficient in BHK-21/C-13 than in BHK-21/WI-2 cells.


Assuntos
Vírus Chikungunya/fisiologia , Expressão Gênica , Interações Hospedeiro-Patógeno , Proteínas de Membrana/genética , Animais , Linhagem Celular , Febre de Chikungunya/genética , Febre de Chikungunya/virologia , Cricetinae , Interações Hospedeiro-Patógeno/genética , Humanos , Proteínas de Membrana/metabolismo
9.
PLoS One ; 16(4): e0249166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33891622

RESUMO

OBJECTIVES: To describe and estimate the frequency of pregnancy outcomes, clinical and laboratory characteristics of vertical transmission of CHIKV in the neonate. STUDY DESIGN: We performed a systematic review evaluating the clinical presentation of perinatally-acquired CHIKV infection in neonates. The search was performed using Medline (via PubMed), LILACS, Web of Science, Scielo, Google Scholar and Open grey to identify studies assessing vertical transmission of CHIKV up to November 3, 2020. There were no search restrictions regarding the study type, the publication date or language. Studies with no documented evidence of CHIKV infection in neonates (negative RT-PCR or absence of IgM) were excluded. RESULTS: From the 227 studies initially identified, 42 were selected as follows: 28 case reports, 7 case series, 2 cross-sectional studies and 5 cohort studies, for a total of 266 CHIKV infected neonates confirmed by serological and/or molecular tests. The vertical transmission rate was 50% in the Reunion Island outbreak, which was the subject of the majority of the studies; the premature delivery were reported in 19 (45.2%) studies; the rate of fetal distress was 19.6% of infected babies and fetal loss occurred in 2% of the cases. Approximately 68.7% of newborns were diagnosed with encephalopathy or encephalitis after perinatally acquired CHIKV. Most of the infected neonates were born healthy, developing CHIKV sepsis clinical syndrome within the first week of life. CONCLUSIONS: We alert neonatologists to the late manifestations of neonatal CHIKV infection, relevant to the management and reduction of morbidity. A limitation of our review was that it was not possible to carry out meta-analysis due to differences in study design and the small number of participants.


Assuntos
Febre de Chikungunya/transmissão , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Vírus Chikungunya/patogenicidade , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/virologia
10.
Front Immunol ; 12: 655743, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868299

RESUMO

Chikungunya fever is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV), for which no licensed vaccines are currently available. Here, we explored several immunization protocols and investigated their immunity and protective effects in mice, with DNA- and virus-like particle (VLP)- vaccines, both alone and in combination. Both DNA and VLP vaccine candidates were developed and characterized, which express CHIKV structural genes (C-E3-E2-6K-E1). Mice were immunized twice, with different protocols, followed by immunological detection and CHIKV Ross challenge. The highest antigen-specific IgG and neutralizing activity were induced by DNA and VLP co-immunization, while the highest cellular immunity was induced by DNA vaccination alone. Although all vaccine groups could protect mice from lethal CHIKV challenge, demonstrated as reduced viral load in various tissues, without weight loss, mice co-immunized with DNA and VLP exhibited the mildest histopathological changes and lowest International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) scores, in comparison to mice with either DNA or VLP vaccination alone. We concluded that co-immunization with DNA and VLP is a promising strategy to inducing better protective immunity against CHIKV infection.


Assuntos
Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Imunização , Vacinas de DNA/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linhagem Celular , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/ultraestrutura , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunização/métodos , Camundongos , Testes de Neutralização , Avaliação de Resultados em Cuidados de Saúde , Vacinas de DNA/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/ultraestrutura , Carga Viral , Vacinas Virais/administração & dosagem
11.
PLoS One ; 16(4): e0249867, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886579

RESUMO

Chikungunya virus (CHIKV) is an arthropod-borne virus transmitted by mosquitoes of the genus Aedes. CHIKV infection causes various rheumatic symptoms, including enthesitis; however, these effects are rarely investigated. The aim of this study was to describe the rheumatic manifestations in CHIKV infection, estimate the prevalence of enthesitis in CHIKV-infected patients, and determine the factors associated with CHIKV-induced enthesitis. We conducted a prospective, observational study in patients with CHIKV infection confirmed by positive RT-PCR or IgM assay from October 2019 to March 2020. Patients with pre-existing inflammatory rheumatic diseases were excluded. A rheumatologist evaluated the demographic and clinical characteristics of the patients, including the number of inflamed joints, enthesitis sites, tendinitis, and tenosynovitis. The Leeds enthesitis index (LEI) and the Maastricht ankylosing spondylitis enthesis score (MASES) were used to evaluate enthesitis sites. Factors associated with enthesitis were determined using logistic regression analysis. One hundred and sixty-four participants diagnosed with CHIKV infection were enrolled. The mean (SD) age of the patients was 48.2 (14) years. The most common pattern of rheumatic manifestations was polyarthritis with or without enthesitis. Enthesitis was observed in 63 patients (38.4%). The most common site of enthesitis was the left lateral epicondyle as assessed by LEI and the posterior superior iliac spine as assessed by MASES. Multivariate analysis indicated that the number of actively inflamed joints and Thai-HAQ score at the initial evaluation were significantly associated with the presence of enthesitis. The main rheumatic manifestations of CHIKV infection were arthritis/arthralgia, with enthesitis as a prominent extraarticular feature. CHIKV infection can cause enthesitis at peripheral and axial sites. We found that enthesitis was associated with a high number of inflamed joints and reduced physical function. These results indicate that the assessment of enthesitis should be considered when monitoring disease activity and as a treatment response parameter in CHIKV-infected patients.


Assuntos
Febre de Chikungunya/diagnóstico , Doenças Reumáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Febre de Chikungunya/complicações , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neuralgia/etiologia , Razão de Chances , Prevalência , Estudos Prospectivos , RNA Viral/análise , RNA Viral/metabolismo , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/etiologia , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/etiologia , Adulto Jovem
12.
Arch Virol ; 166(7): 1913-1920, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33907861

RESUMO

Chikungunya virus (CHIKV) infection is endemic in many different countries. CHIKV outbreaks are emerging in new areas and re-emerging in previously exposed geographical regions, thus making it a significant public health concern. CHIKV infections are often clinically inapparent, especially in children, which poses a challenge to testing and evaluating any vaccine. During CHIKV infection, CHIKV-specific antibodies are produced, and some of these antibodies can neutralize viruses released from infected cells before they can enter uninfected cells. In this study, we evaluated IgG binding and neutralizing antibody responses in paired serum samples from CHIKV-infected children and those with other febrile illness, using a recombinant truncated E2 protein and whole CHIKV particles as test antigens. Antibody detection using the truncated E2 protein showed a significant overlap between CHIKV-infected subjects and those with other febrile illnesses. This overlap was greater when binding antibody titers were determined using fixed CHIKV particles as the test antigen. Acute- and convalescent-phase sera collected from children after CHIKV infection showed significant differences in their neutralizing capacity. The neutralizing and binding antibody response showed a significant positive correlation. We detected IgG antibodies in most cases during the acute phase of infection. This was observed at two different geographical locations, one of which is not considered highly endemic. Conventional wisdom would suggest this to be a marker of re-infection (secondary infection). However, dissenting opinions have been voiced in other viral diseases (such as Ebola) where studies have detected IgG in acute illness. In the absence of any significant body of work documenting secondary CHIKV infections, we believe further work is needed to understand the early IgG response that we observed.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Imunoglobulina G/imunologia , Febre de Chikungunya/virologia , Criança , Feminino , Humanos , Índia , Masculino , Proteínas do Envelope Viral/imunologia
13.
Viruses ; 13(3)2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806267

RESUMO

Using reverse genetics, we analyzed a chikungunya virus (CHIKV) isolate of the Indian Ocean lineage lacking direct repeat (DR) elements in the 3' untranslated region, namely DR1a and DR2a. While this deletion mutant CHIKV-∆DR exhibited growth characteristics comparable to the wild-type virus in Baby Hamster Kidney cells, replication of the mutant was reduced in Aedes albopictus C6/36 and Ae. aegypti Aag2 cells. Using oral and intrathoracic infection of mosquitoes, viral infectivity, dissemination, and transmission of CHIKV-∆DR could be shown for the well-known CHIKV vectors Ae. aegypti and Ae. albopictus. Oral infection of Ae. vexans and Culex pipiens mosquitoes with mutant or wild-type CHIKV showed very limited infectivity. Dissemination, transmission, and transmission efficiencies as determined via viral RNA in the saliva were slightly higher in Ae. vexans for the wild-type virus than for CHIKV-∆DR. However, both Ae. vexans and Cx. pipiens allowed efficient viral replication after intrathoracic injection confirming that the midgut barrier is an important determinant for the compromised infectivity after oral infection. Transmission efficiencies were neither significantly different between Ae. vexans and Cx. pipiens nor between wild-type and CHIKV-∆DR. With a combined transmission efficiency of 6%, both Ae. vexans and Cx. pipiens might serve as potential vectors in temperate regions.


Assuntos
Aedes/virologia , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Culex/virologia , Mosquitos Vetores/virologia , Regiões 3' não Traduzidas , Animais , Chlorocebus aethiops , Cricetinae , Genes Virais , Células Vero
14.
Viruses ; 13(4)2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806250

RESUMO

The Asian tiger mosquito Aedes albopictus is contributing to the (re)-emergence of Chikungunya virus (CHIKV). To gain insights into the molecular underpinning of viral persistence, which renders a mosquito a life-long vector, we coupled small RNA and whole genome sequencing approaches on carcasses and ovaries of mosquitoes sampled 14 days post CHIKV infection and investigated the profile of small RNAs and the presence of vDNA fragments. Since Aedes genomes harbor nonretroviral Endogenous Viral Elements (nrEVEs) which confers tolerance to cognate viral infections in ovaries, we also tested whether nrEVEs are formed after CHIKV infection. We show that while small interfering (si)RNAs are evenly distributed along the full viral genome, PIWI-interacting (pi)RNAs mostly arise from a ~1000 bp window, from which a unique vDNA fragment is identified. CHIKV infection does not result in the formation of new nrEVEs, but piRNAs derived from existing nrEVEs correlate with differential expression of an endogenous transcript. These results demonstrate that all three RNAi pathways contribute to the homeostasis during the late stage of CHIKV infection, but in different ways, ranging from directly targeting the viral sequence to regulating the expression of mosquito transcripts and expand the role of nrEVEs beyond immunity against cognate viruses.


Assuntos
Aedes/virologia , Vírus Chikungunya/genética , DNA Viral/genética , Genoma Viral , Pequeno RNA não Traduzido/genética , Integração Viral/genética , Animais , Febre de Chikungunya/imunologia , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Feminino , Mosquitos Vetores/virologia , Ovário/virologia , Sequenciamento Completo do Genoma
15.
Viruses ; 13(4)2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806252

RESUMO

Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40-50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.


Assuntos
Feto Abortado/patologia , Aborto Espontâneo/patologia , Aborto Espontâneo/virologia , Febre de Chikungunya/complicações , Transmissão Vertical de Doenças Infecciosas , Feto Abortado/virologia , Adulto , Anticorpos Antivirais/sangue , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Feminino , Técnicas Histológicas , Humanos , Imunoglobulina M/sangue , Gravidez
16.
PLoS Negl Trop Dis ; 15(4): e0009337, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33909610

RESUMO

BACKGROUND: As the three major arthropod-borne viruses, dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) are posing a growing threat to global public health and socioeconomic development. Our study aimed to systematically review the global seroprevalences of these arboviruses from existing publications. METHODS: Articles published between Jan 01, 2000 and Dec 31, 2019 in the databases of Embase, Pubmed and Web of Science were searched and collected. Countries or areas with known local presence of Aedes vector mosquitoes were included. Random effects model was utilized to estimate the pooled seroprevalences and the proportion of inapparent infection. RESULTS: Out of 1375, a total of 133 articles involving 176,001 subjects were included for our analysis. The pooled seroprevalences of DENV, CHIKV and ZIKV were 38%, 25% and 18%, respectively; and their corresponding proportions of inapparent infections were 80%, 40% and 50%. The South-East Asia Region had the highest seroprevalences of DENV and CHIKV, while the Region of the Americas had the highest seroprevalence of ZIKV. The seroprevalences of DENV and CHIKV were similar when comparing developed and developing countries, urban and rural areas, or among different populations. In addition, we observed a decreased global seroprevalences in the new decade (2010-2019) comparing to the decade before (2000-2009) for CHIKV. For ZIKV, the positive rates tested with the nucleic acid detection method were lower than those tested with the antibody detection method. Lastly, numerous cases of dual seropositivity for CHIKV and DENV were reported. CONCLUSIONS: Our results revealed a varied prevalence of arbovirus infections in different geographical regions and countries, and the inapparent infection accounted an unneglected portion of infections that requires more attention. This study will shed lights on our understanding of the true burden of arbovirus infections and promote appropriate vaccination in the future.


Assuntos
Aedes/virologia , Febre de Chikungunya/epidemiologia , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Animais , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/fisiologia , Saúde Global , Humanos , Mosquitos Vetores/virologia , Estudos Soroepidemiológicos , Zika virus/fisiologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
17.
PLoS Negl Trop Dis ; 15(4): e0009387, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33930028

RESUMO

BACKGROUND: The public health impact of Chikungunya virus (CHIKV) is often underestimated. Usually considered a mild condition of short duration, recent outbreaks have reported greater incidence of severe illness, fatality, and longer-term disability. In 2018/19, Eastern Sudan experienced the largest epidemic of CHIKV in Africa to date, affecting an estimated 487,600 people. Known locally as Kankasha, this study examines clinical characteristics, risk factors, and phylogenetics of the epidemic in Kassala City. METHODOLOGY/PRINCIPAL FINDINGS: A prospective cohort of 102 adults and 40 children presenting with chikungunya-like illness were enrolled at Kassala Teaching Hospital in October 2018. Clinical information, socio-demographic data, and sera samples were analysed to confirm diagnosis, characterise illness, and identify viral strain. CHIKV infection was confirmed by real-time reverse transcription-PCR in 84.5% (120/142) of participants. Nine (7.5%) CHIKV-positive participants had concurrent Dengue virus (DENV) infection; 34/118 participants (28.8%) had a positive Rapid Diagnostic Test for Plasmodium falciparum; six (5.0%) had haemorrhagic symptoms including two children with life-threatening bleeding. One CHIKV-positive participant died with acute renal injury. Age was not associated with severity of illness although CHIKV-infected participants were younger (p = 0.003). Two to four months post-illness, 63% of adults available for follow-up (30) were still experiencing arthralgia in one or more joints, and 11% remained moderately disabled on Rapid3 assessment. Phylogenetic analysis showed all CHIKV sequences from this study belonged to a single clade within the Indian Ocean Lineage (IOL) of the East/Central/South African (ECSA) genotype. History of contact with an infected person was the only factor associated with infection (p = 0.01), and likely related to being in the same vector environment. CONCLUSIONS/SIGNIFICANCE: Vulnerability to CHIKV remains in Kassala and elsewhere in Sudan due to widespread Aedes aegypti presence and mosquito-fostering household water storage methods. This study highlights the importance of increasing awareness of the severity and impact of CHIKV outbreaks, and the need for urgent actions to reduce transmission risk in households.


Assuntos
Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Surtos de Doenças , Adolescente , Adulto , Aedes/virologia , Animais , Febre de Chikungunya/mortalidade , Vírus Chikungunya/isolamento & purificação , Criança , Pré-Escolar , Epidemias , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Mosquitos Vetores/virologia , Filogenia , Estudos Prospectivos , Sudão/epidemiologia , Adulto Jovem
18.
Biomed Res Int ; 2021: 6623400, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33855075

RESUMO

Chikungunya (CHIK) is a reemerging arboviral disease caused by chikungunya virus (CHIKV) infection. The disease is clinically hallmarked by prolonged debilitating joint pain. Currently, there is no specific antiviral medication nor commercial vaccine available for treatment of the disease, which makes the discovery or development of specific anti-CHIKV compounds a priority. Ginger (Zingiber officinale Roscoe) is widely known for its various health benefits. The compound [6]-gingerol is the main active ingredient found in ginger. This study sought to determine the potential of [6]-gingerol antiviral activity against CHIKV infection using in vitro human hepatocyte HepG2 cells. The antiviral activity mechanism was investigated using direct virucidal and four indirect (pre-, post-, full-, and prevention) treatment assays. [6]-Gingerol showed weak virucidal activity but significant indirect antiviral activity against CHIKV through post- and full treatment with IC50 of 0.038 mM and 0.031 mM, respectively, without showing cell cytotoxicity. The results indicated that [6]-gingerol inhibits CHIKV infection through suppression of viral replication. Together, this study confirms the potential use of [6]-gingerol for CHIK antiviral compound.


Assuntos
Catecóis/farmacologia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Álcoois Graxos/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/farmacologia , Catecóis/química , Morte Celular/efeitos dos fármacos , Linhagem Celular , Vírus Chikungunya/efeitos dos fármacos , Álcoois Graxos/química , Humanos
19.
PLoS Negl Trop Dis ; 15(4): e0009267, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33836004

RESUMO

BACKGROUND: In 2014, a first outbreak of chikungunya hit the Caribbean area where chikungunya virus (CHIKV) had never circulated before. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional study to measure the seroprevalence of CHIKV immediately after the end of the 2014 outbreak in HIV-infected people followed up in two clinical cohorts at the University hospitals of Guadeloupe and Martinique. Study patients were identified during the first months of 2015 and randomly selected to match the age and sex distribution of the general population in the two islands. They were invited to complete a survey that explored the symptoms consistent with chikungunya they could have developed during 2014 and to have a blood sample drawn for CHIKV serology. The study population consisted of 377 patients (198 in Martinique and 179 in Guadeloupe, 178 men and 199 women), 182 of whom reported they had developed symptoms consistent with chikungunya. CHIKV serology was positive in 230 patients, which accounted for an overall seroprevalence rate of 61% [95%CI 56-66], with only 153 patients who reported symptoms consistent with chikungunya. Most frequent symptoms included arthralgia (94.1%), fever (73.2%), myalgia (53.6%), headache (45.8%), and skin rash (26.1%). CONCLUSIONS/SIGNIFICANCE: This study showed that the seroprevalence of CHIKV infection was 61% after the 2014 outbreak, with one third of asymptomatic infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT02553369.


Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya/isolamento & purificação , Surtos de Doenças , Infecções por HIV/epidemiologia , Adulto , Artralgia/epidemiologia , Febre de Chikungunya/virologia , Estudos Transversais , Exantema/epidemiologia , Feminino , Febre/epidemiologia , Guadalupe/epidemiologia , Cefaleia/epidemiologia , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Mialgia/epidemiologia , Estudos Prospectivos , Estudos Soroepidemiológicos
20.
PLoS Negl Trop Dis ; 15(4): e0009289, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33878115

RESUMO

BACKGROUND: Chikungunya is an arbovirus, transmitted by Aedes mosquitoes, which emerged in the Americas in 2013 and spread rapidly to almost every country on this continent. In Brazil, where the first cases were detected in 2014, it currently has reached all regions of this country and more than 900,000 cases were reported. The clinical spectrum of chikungunya ranges from an acute self-limiting form to disabling chronic forms. The purpose of this study was to estimate the seroprevalence of chikungunya infection in a large Brazilian city and investigate the association between viral circulation and living condition. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based ecological study in selected Sentinel Areas (SA) through household interviews and a serologic survey in 2016/2017. The sample was of 1,981 individuals randomly selected. The CHIKV seroprevalence was 22.1% (17.1 IgG, 2.3 IgM, and 1.4 IgG and IgM) and varied between SA from 2.0% to 70.5%. The seroprevalence was significantly lower in SA with high living conditions compared to SA with low living condition. There was a positive association between CHIKV seroprevalence and population density (r = 0.2389; p = 0.02033). CONCLUSIONS/SIGNIFICANCE: The seroprevalence in this city was 2.6 times lower than the 57% observed in a study conducted in the epicentre of the CHIKV epidemic of this same urban centre. So, the herd immunity in this general population, after four years of circulation of this agent is relatively low. It indicates that CHIKV transmission may persist in that city, either in endemic form or in the form of a new epidemic, because the vector infestation is persistent. Besides, the significantly lower seroprevalences in SA of higher Living Condition suggest that beyond the surveillance of the disease, vector control and specific actions of basic sanitation, the reduction of the incidence of this infection also depends on the improvement of the general living conditions of the population.


Assuntos
Anticorpos Antivirais/sangue , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/transmissão , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/imunologia , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Surtos de Doenças , Feminino , Humanos , Imunidade Coletiva , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância da População , Estudos Soroepidemiológicos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...