RESUMO
We describe the circulation of Saint Louis encephalitis virus (SLEV) in two Brazilian States during outbreaks of Dengue and Zika viruses. We detected the virus in a patient from Araraquara, State of São Paulo, and in patients and in a mosquito pool of Culex quinquefasciatus from Sinop, State of Mato Grosso. Phylogenetic analysis grouped samples from this study within genotype V, which are closely related to other strains that previously circulated in other parts of the country. Genotype V seems to have established circulation in Brazil.
Assuntos
Culicidae/virologia , Vírus da Encefalite de St. Louis/genética , Encefalite de St. Louis/virologia , Genótipo , Adolescente , Animais , Brasil/epidemiologia , Criança , Pré-Escolar , Dengue/epidemiologia , Surtos de Doenças , Vírus da Encefalite de St. Louis/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Filogenia , Infecção por Zika virus/epidemiologiaRESUMO
BACKGROUND: St. Louis encephalitis virus (SLEV) is endemic and autochthonous on the American continent. Culex pipiens quinquefasciatus is a vector of SLEV; however, Culex interfor and Culex saltanensis have also been found to be naturally infected with SLEV. The aim of this study was to determine the vector competence of C. interfor and C. saltanensis for SLEV from Argentina compared with C. p. quinquefasciatus. METHODS: Female of the Culex species were orally infected by feeding on viraemic chicks that had been inoculated with SLEV. Abdomens, legs and saliva blood-fed mosquitoes were analysed by viral plaque assay. RESULTS: Mosquitoes were susceptible to orally acquired infection, dissemination and transmission of SLEV in the saliva. CONCLUSIONS: Our results demonstrate that C. saltanensis and C. interfor are susceptible to SLEV and competent for its transmission.
Assuntos
Culex/virologia , Vírus da Encefalite de St. Louis , Encefalite de St. Louis/transmissão , Mosquitos Vetores/virologia , Animais , Argentina , Culicidae , Encefalite de St. Louis/diagnóstico , Encefalite de St. Louis/virologia , Feminino , HumanosRESUMO
We evaluated the seroprevalence of Saint Louis encephalitis virus (SLEV) and West Nile virus (WNV) in dogs and cats in Córdoba, Argentina. Monotypic and heterotypic serological patterns were differentiated by means of a neutralization test. The SLEV seroprevalence in dogs was 14.6% (44/302; 100% monotypic). Two out of 94 (2.1%, 100% monotypic) cats were positive for WNV only. Four dogs (1.3%) exhibited neutralizing antibody titers against SLEV and WNV. During the study, three dogs seroconverted to SLEV. Our study demonstrates that pets were useful for detecting viral activity and could be considered as sentinels in the local surveillance of SLEV and WNV.
Assuntos
Anticorpos Antivirais/sangue , Doenças do Gato/sangue , Doenças do Cão/sangue , Vírus da Encefalite de St. Louis/imunologia , Encefalite de St. Louis/veterinária , Animais de Estimação/sangue , Febre do Nilo Ocidental/veterinária , Vírus do Nilo Ocidental/imunologia , Animais , Argentina , Doenças do Gato/epidemiologia , Doenças do Gato/virologia , Gatos , Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Cães , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/sangue , Encefalite de St. Louis/epidemiologia , Encefalite de St. Louis/virologia , Animais de Estimação/virologia , Estudos Soroepidemiológicos , Febre do Nilo Ocidental/sangue , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/isolamento & purificaçãoRESUMO
St. Louis encephalitis virus (SLEV) is a flavivirus that circulates in an enzootic cycle between birds and mosquitoes and can also infect humans to cause febrile disease and sometimes encephalitis. Although SLEV is endemic to the United States, no activity was detected in California during the years 2004 through 2014, despite continuous surveillance in mosquitoes and sentinel chickens. In 2015, SLEV-positive mosquito pools were detected in Maricopa County, Arizona, concurrent with an outbreak of human SLEV disease. SLEV-positive mosquito pools were also detected in southeastern California and Nevada in summer 2015. From 2016 to 2018, SLEV was detected in mosquito pools throughout southern and central California, Oregon, Idaho, and Texas. To understand genetic relatedness and geographic dispersal of SLEV in the western United States since 2015, we sequenced four historical genomes (3 from California and 1 from Louisiana) and 26 contemporary SLEV genomes from mosquito pools from locations across the western US. Bayesian phylogeographic approaches were then applied to map the recent spread of SLEV. Three routes of SLEV dispersal in the western United States were identified: Arizona to southern California, Arizona to Central California, and Arizona to all locations east of the Sierra Nevada mountains. Given the topography of the Western United States, these routes may have been limited by mountain ranges that influence the movement of avian reservoirs and mosquito vectors, which probably represents the primary mechanism of SLEV dispersal. Our analysis detected repeated SLEV introductions from Arizona into southern California and limited evidence of year-to-year persistence of genomes of the same ancestry. By contrast, genetic tracing suggests that all SLEV activity since 2015 in central California is the result of a single persistent SLEV introduction. The identification of natural barriers that influence SLEV dispersal enhances our understanding of arbovirus ecology in the western United States and may also support regional public health agencies in implementing more targeted vector mitigation efforts to protect their communities more effectively.
Assuntos
Culicidae/virologia , Vírus da Encefalite de St. Louis/classificação , Vírus da Encefalite de St. Louis/genética , Encefalite de St. Louis/epidemiologia , Encefalite de St. Louis/virologia , Mosquitos Vetores/virologia , Animais , Teorema de Bayes , Surtos de Doenças , Genoma Viral , Humanos , Filogenia , Filogeografia , Estados Unidos/epidemiologia , Sequenciamento Completo do GenomaRESUMO
West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related mosquito-borne flaviviruses that cause clinical disease ranging from febrile illness to encephalitis. The standard for serological diagnosis is immunoglobulin M (IgM) testing followed by confirmatory plaque reduction neutralization test (PRNT) to differentiate the infecting virus. However, the PRNT is time-consuming and requires manipulation of live virus. During concurrent WNV and SLEV outbreaks in Arizona in 2015, we assessed use of a diagnostic algorithm to simplify testing. It incorporated WNV and SLEV ratios based on positive-to-negative (P/N) values derived from the IgM antibody-capture enzyme-linked immunosorbent assay. We compared each sample's ratio-based result with the confirmed WNV or SLEV sample result indicated by PRNT or PCR testing. We analyzed data from 70 patients with 77 serum and cerebrospinal fluid samples, including 53 patients with confirmed WNV infection and 17 patients with confirmed SLEV infection. Both WNV and SLEV ratios had specificity ≥95%, indicating a high likelihood that each ratio was correctly identifying the infecting virus. The SLEV ratio sensitivity of 30% was much lower than the WNV ratio sensitivity of 91%, likely because of higher cross-reactivity of SLEV antibodies and generation of lower P/N values. The standard for serological diagnosis of WNV and SLEV infections remains IgM testing followed by PRNT. However, these results suggest the ratios could potentially be used as part of a diagnostic algorithm in outbreaks to substantially reduce the need for PRNTs.
Assuntos
Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina M/sangue , Febre do Nilo Ocidental/diagnóstico , Vírus do Nilo Ocidental/isolamento & purificação , Arizona/epidemiologia , Surtos de Doenças , Encefalite de St. Louis/epidemiologia , Encefalite de St. Louis/virologia , Humanos , Sensibilidade e Especificidade , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/virologiaRESUMO
Saint Louis encephalitis virus (SLEV) is a mosquito-borne flavivirus that occurs throughout the Americas, and is considered a public health threat. In Brazil, SLEV has been detected from human cases associated with dengue-like disease, but no neurological symptoms were reported. Furthermore, the epidemiology of SLEV in human populations is still poorly explored in the country. We reported serological and molecular detection of SLEV in a healthy population of equids and humans from rural areas in Southeast Brazil. A plaque reduction neutralization test was applied, and neutralizing antibodies were detected in 11 individuals (4.6%) and 60 horses (21.5%). A qPCR targeting the 5'UTR region and reverse transcription-PCR (RT-PCR) targeting the non-structural protein (NS5) gene were performed and three individuals tested positive in both assays. Subsequent phylogenetic analysis confirmed SLEV circulation and its findings suggest the occurrence of an asymptomatic or subclinical presence in human and animal cases, correlating with the risks for outbreaks and consequently burden of SLEV infections to public health. Preventive strategies should include improved surveillance in regions with a high probability of SLEV occurrence, improvement in diagnostic methods, and evaluation of exposure/risk factors that can favor SLEV emergence.
Assuntos
Vírus da Encefalite de St. Louis , Encefalite de St. Louis , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Infecções Assintomáticas , Brasil/epidemiologia , Dengue/diagnóstico , Diagnóstico Diferencial , Vírus da Encefalite de St. Louis/genética , Vírus da Encefalite de St. Louis/imunologia , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/diagnóstico , Encefalite de St. Louis/transmissão , Encefalite de St. Louis/veterinária , Encefalite de St. Louis/virologia , Flaviviridae/isolamento & purificação , Genes Virais , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/virologia , Cavalos , Humanos , Testes de Neutralização , Filogenia , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Free-ranging non-human primates (NHPs) can host a variety of pathogenic microorganisms, such as arboviruses, which include the yellow fever virus (YFV). This study aimed to detect the circulation of YF and other arboviruses in three wild Alouatta caraya populations in forests in southern Brazil. METHODS: We collected 40 blood and serum samples from 26 monkeys captured/recaptured up to four times from 2014 to 2016, searching for evidence of arboviruses by virus isolation, PCR, and neutralization tests. RESULTS: Viral isolation and genome detection were negative; however, we detected neutralizing antibodies against the Saint Louis, Ilhéus, and Icoaraci viruses in three NHPs. CONCLUSIONS: Saint Louis Encephalitis, Ilhéus, and Icoaraci viruses circulated recently in the region. Future studies should investigate the role of NHPs, other vertebrate hosts and wild vectors in the region's arbovirus circulation and the potential risks of the arboviruses to wildlife, domestic animals, and humans.
Assuntos
Alouatta caraya , Encefalite de St. Louis/veterinária , Infecções por Flavivirus/veterinária , Doenças dos Macacos/epidemiologia , Febre do Vale de Rift/epidemiologia , Animais , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/epidemiologia , Encefalite de St. Louis/virologia , Flavivirus/isolamento & purificação , Infecções por Flavivirus/epidemiologia , Infecções por Flavivirus/virologia , Febre do Vale de Rift/virologia , Vírus da Febre do Vale do Rift/isolamento & purificaçãoRESUMO
Saint Louis encephalitis virus (SLEV) and West Nile virus (WNV) are two of the major causes of arboviral encephalitis in the Americas. The co-circulation of related flaviviruses in the Americas and prior vaccination against flaviviruses pose problems to the diagnostic specificity of serological assays due to the development of cross-reactive antibodies. An accurate diagnosis method capable of differentiating these related viruses is needed. NS1 is a glycosylated, nonstructural protein, of about 46â¯kDa which has a highly conserved structure. Anti-NS1 antibodies can be detected within 4-8 days after the initial exposure and NS1 is the least cross-reactive of the flaviviral antigens. This study was aimed to generate SLEV and WNV NS1 recombinants proteins for the development of a flavivirus diagnostic test. Local Argentinian isolates were used as the source of NS1 gene cloning, expression, and purification. The protein was expressed in Escherichia coli as inclusion bodies and further purified by metal-chelating affinity chromatography (IMAC) under denaturing conditions. Human sera from SLEV and WNV positive cases showed reactivity to the recombinant NS1 proteins by western blot. The unfolded NS1 proteins were also used as immunogens. The polyclonal antibodies elicited in immunized mice recognized the two recombinant proteins with differential reactivity.
Assuntos
Anticorpos Antivirais/biossíntese , Antígenos Virais/imunologia , Vírus da Encefalite de St. Louis/imunologia , Encefalite de St. Louis/diagnóstico , Proteínas não Estruturais Virais/imunologia , Febre do Nilo Ocidental/diagnóstico , Vírus do Nilo Ocidental/imunologia , Animais , Especificidade de Anticorpos , Antígenos Virais/biossíntese , Antígenos Virais/genética , Argentina , Western Blotting , Cromatografia de Afinidade , Clonagem Molecular , Reações Cruzadas , Diagnóstico Diferencial , Vírus da Encefalite de St. Louis/química , Vírus da Encefalite de St. Louis/genética , Encefalite de St. Louis/imunologia , Encefalite de St. Louis/virologia , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Corpos de Inclusão/química , Camundongos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Solubilidade , Proteínas não Estruturais Virais/biossíntese , Proteínas não Estruturais Virais/genética , Febre do Nilo Ocidental/imunologia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/química , Vírus do Nilo Ocidental/genéticaRESUMO
We summarize and analyze historical and current data regarding the reemergence of St. Louis encephalitis virus (SLEV; genus Flavivirus) in the Americas. Historically, SLEV caused encephalitis outbreaks in the United States; however, it was not considered a public health concern in the rest of the Americas. After the introduction of West Nile virus in 1999, activity of SLEV decreased considerably in the United States. During 2014-2015, SLEV caused a human outbreak in Arizona and caused isolated human cases in California in 2016 and 2017. Phylogenetic analyses indicate that the emerging SLEV in the western United States is related to the epidemic strains isolated during a human encephalitis outbreak in Córdoba, Argentina, in 2005. Ecoepidemiologic studies suggest that the emergence of SLEV in Argentina was caused by the introduction of a more pathogenic strain and increasing populations of the eared dove (amplifying host).
Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Vírus da Encefalite de St. Louis/fisiologia , Encefalite de St. Louis/epidemiologia , Doenças Transmissíveis Emergentes/história , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Surtos de Doenças , Vírus da Encefalite de St. Louis/classificação , Vírus da Encefalite de St. Louis/genética , Encefalite de St. Louis/história , Encefalite de St. Louis/transmissão , Encefalite de St. Louis/virologia , Geografia Médica , História do Século XX , História do Século XXI , Humanos , Filogenia , América do Sul/epidemiologia , Estados Unidos/epidemiologiaAssuntos
Infecções por Bunyaviridae/transmissão , Culicidae/virologia , Vírus da Encefalite de St. Louis/fisiologia , Encefalite de St. Louis/transmissão , Mosquitos Vetores/virologia , Orthobunyavirus/fisiologia , Animais , Argentina , Infecções por Bunyaviridae/virologia , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/virologia , Feminino , Humanos , Orthobunyavirus/isolamento & purificação , Sorogrupo , ZoonosesRESUMO
St. Louis encephalitis virus (SLEV), an arthropod-borne flavivirus, can cause disease presentations ranging from mild febrile illness through severe encephalitis. We reviewed U.S. national SLEV surveillance data for 2003 through 2017, including human disease cases and nonhuman infections. Over the 15-year period, 198 counties from 33 states and the District of Columbia reported SLEV activity; 94 (47%) of those counties reported SLEV activity only in nonhuman species. A total of 193 human cases of SLEV disease were reported, including 148 cases of neuroinvasive disease. A median of 10 cases were reported per year. The national average annual incidence of reported neuroinvasive disease cases was 0.03 per million. States with the highest average annual incidence of reported neuroinvasive disease cases were Arkansas, Arizona, and Mississippi. No large outbreaks occurred during the reporting period. The most commonly reported clinical syndromes were encephalitis (N = 116, 60%), febrile illness (N = 35, 18%), and meningitis (N = 25, 13%). Median age of cases was 57 years (range 2-89 years). The case fatality rate was 6% (11/193) and all deaths were among patients aged > 45 years with neuroinvasive disease. Nonhuman surveillance data indicated wider SLEV activity in California, Nevada, and Florida than the human data alone suggested. Prevention depends on community efforts to reduce mosquito populations and personal protective measures to decrease exposure to mosquitoes.
Assuntos
Culicidae/virologia , Vírus da Encefalite de St. Louis/patogenicidade , Encefalite de St. Louis/epidemiologia , Encefalite de St. Louis/transmissão , Mosquitos Vetores/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/mortalidade , Encefalite de St. Louis/virologia , Monitoramento Epidemiológico , Feminino , Febre/fisiopatologia , Humanos , Incidência , Masculino , Meningite/fisiopatologia , Pessoa de Meia-Idade , Análise de Sobrevida , Estados Unidos/epidemiologiaRESUMO
St.Louis encephalitis virus (SLEV) is an emerging human pathogen flavivirus in Argentina. Recently, it has reemerged in the United States. We evaluated the role as amplifying host of six resident bird species and analyzed their capacity as host during the 2005 encephalitis outbreak of SLEV in Córdoba. Eared Dove, Picui Ground Dove, and House Sparrow were the three species with highest host competence index. At a city level, Eared Dove and Picui Ground Dove were the most important amplifying hosts during the 2005 SLEV human outbreak in Córdoba city. This finding highlighted important differences in the SLEV ecology between Argentina and the United States. Characterizing and evaluating the SLEV hosts contribute to our knowledge about its ecology and could help us to understand the causes that promote its emergence as a human pathogen in South America.
Assuntos
Columbidae/virologia , Surtos de Doenças , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/epidemiologia , Pardais/virologia , Animais , Argentina/epidemiologia , Reservatórios de Doenças/virologia , Encefalite de St. Louis/transmissão , Encefalite de St. Louis/virologia , Humanos , Carga ViralRESUMO
We used unbiased metagenomic next-generation sequencing to diagnose a fatal case of meningoencephalitis caused by St. Louis encephalitis virus in a patient from California in September 2016. This case is associated with the recent 2015-2016 reemergence of this virus in the southwestern United States.
Assuntos
Broncopneumonia/diagnóstico , Vírus da Encefalite de St. Louis/genética , Encefalite de St. Louis/diagnóstico , Genoma Viral , Linfoma de Célula do Manto/diagnóstico , Metagenoma , Idoso , Broncopneumonia/patologia , California , Vírus da Encefalite de St. Louis/classificação , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/líquido cefalorraquidiano , Encefalite de St. Louis/patologia , Encefalite de St. Louis/virologia , Evolução Fatal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma de Célula do Manto/patologia , Masculino , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In summer 2015, three unrelated solid organ transplant recipients in Phoenix, Arizona, had meningoencephalitis suggestive of West Nile virus (WNV) infection. Testing was inconclusive but was later confirmed as St. Louis encephalitis (SLE). We retrospectively reviewed clinical manifestations, treatment, and outcomes of these transplant recipients. Common symptoms were fever, rigors, diarrhea, headache, and confusion. One patient died 3 days after hospitalization. Therapy for the other two patients was initiated with interferon α-2b (IFN) and intravenous IgG (IVIG; IFN plus IVIG in combination). Both patients tested positive for WNV by serologic assay, but SLE virus (SLEV) infection was later confirmed by plaque reduction neutralization test at a reference laboratory. Clinical improvement was observed within 72 h after initiation of IFN plus IVIG. SLEV has been an uncommon cause of neuroinvasive disease in the United States. Accurate, timely diagnosis is hindered because of clinical presentation similar to neuroinvasive WNV and SLE, serologic cross-reactivity, and lack of a commercially available serologic assay for SLEV. There is currently no approved therapy for flaviviral neuroinvasive disease. Anecdotal reports indicate varying success with IFN, IVIG, or IFN plus IVIG in WNV neuroinvasive disease. The same regimen might be of value for immunocompromised persons with neuroinvasive SLEV infection.
Assuntos
Antivirais/uso terapêutico , Surtos de Doenças , Vírus da Encefalite de St. Louis/efeitos dos fármacos , Encefalite de St. Louis/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Órgãos , Idoso , Anticorpos Antivirais/sangue , Encefalite de St. Louis/tratamento farmacológico , Encefalite de St. Louis/virologia , Seguimentos , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Transplantados , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. METHODS: To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. RESULTS: Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. CONCLUSIONS: Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection.
Assuntos
Citocinas/metabolismo , Modelos Animais de Doenças , Vírus da Encefalite de St. Louis/fisiologia , Encefalite de St. Louis/patologia , Análise de Variância , Animais , Linhagem Celular Transformada , Encefalite de St. Louis/virologia , Peroxidase de Eosinófilo/metabolismo , Hexosaminidases/metabolismo , Leucócitos/metabolismo , Leucócitos/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Fatores de Tempo , Carga ViralRESUMO
Saint Louis encephalitis virus (SLEV) reemerged in South America, and caused encephalitis outbreaks at the beginning of the 21st century. To enhance our knowledge about SLEV virulence, we performed comparative pathogenesis studies in Swiss albino mice inoculated with two different variants, the epidemic strain CbaAr-4005 and the non-epidemic strain CorAn-9275. Only the infection of mice with SLEV strain CbaAr-4005 resulted in high viremia, invasion of peripheral tissues including the lungs, kidney, and spleen, and viral neuroinvasion. This was associated with inflammatory pathology in the lungs, spleen, and brain as well as morbidity and mortality. In contrast, neither signs of desease nor viral replication were observed in mice infected with strain CorAn-9275. Interestingly, important loss of B cells and development of altered germinal centers (GC) were detected in the spleen of mice infected with strain CbaAr-4005, whereas mice infected with SLEV CorAn-9275 developed prominent GC with conserved follicular architecture, and neutralizing antibodies.
Assuntos
Encéfalo/virologia , Vírus da Encefalite de St. Louis/patogenicidade , Encefalite de St. Louis/epidemiologia , Rim/virologia , Pulmão/virologia , Baço/virologia , Tropismo Viral/fisiologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Argentina/epidemiologia , Linfócitos B/citologia , Vírus da Encefalite de St. Louis/classificação , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/mortalidade , Encefalite de St. Louis/virologia , Contagem de Linfócitos , Camundongos , Carga Viral , Viremia/virologia , Replicação Viral/fisiologiaRESUMO
The error rate of the RNA-dependent RNA polymerase (RdRp) of RNA viruses is important in maintaining genetic diversity for viral adaptation and fitness. Numerous studies have shown that mutagen-resistant RNA virus variants display amino acid mutations in the RdRp and other replicase subunits, which in turn exhibit an altered fidelity phenotype affecting viral fitness, adaptability and pathogenicity. St. Louis encephalitis virus (SLEV), like its close relative West Nile virus, is a mosquito-borne flavivirus that has the ability to cause neuroinvasive disease in humans. Here, we describe the successful generation of multiple ribavirin-resistant populations containing a shared amino acid mutation in the SLEV RdRp (E416K). These E416K mutants also displayed resistance to the antiviral T-1106, an RNA mutagen similar to ribavirin. Structural modelling of the E416K polymerase mutation indicated its location in the pinky finger domain of the RdRp, distant from the active site. Deep sequencing of the E416K mutant revealed lower genetic diversity than wild-type SLEV after growth in both vertebrate and invertebrate cells. Phenotypic characterization showed that E416K mutants displayed similar or increased replication in mammalian cells, as well as modest attenuation in mosquito cells, consistent with previous work with West Nile virus high-fidelity variants. In addition, attenuation was limited to mosquito cells with a functional RNA interference response, suggesting an impaired capacity to escape RNA interference could contribute to attenuation of high-fidelity variants. Our results provide increased evidence that RNA mutagen resistance arises through modulation of the RdRp and give further insight into the consequences of altered fidelity of flaviviruses.
Assuntos
Antivirais/farmacologia , Farmacorresistência Viral/genética , Vírus da Encefalite de St. Louis/efeitos dos fármacos , Vírus da Encefalite de St. Louis/genética , Encefalite de St. Louis/virologia , Mutagênicos/farmacologia , RNA Polimerase Dependente de RNA/genética , Ribavirina/farmacologia , Proteínas não Estruturais Virais/genética , Substituição de Aminoácidos , Vírus da Encefalite de St. Louis/enzimologia , Ácido Glutâmico/genética , Células HeLa , Humanos , Lisina/genética , Modelos Moleculares , Mutação , Nucleosídeos/farmacologia , Domínios Proteicos , Pirazinas/farmacologia , RNA Polimerase Dependente de RNA/química , Proteínas não Estruturais Virais/químicaRESUMO
Not available.
Assuntos
Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/virologia , Meningite Asséptica/virologia , Animais , Culex/virologia , Diagnóstico Diferencial , Vírus da Encefalite de St. Louis/patogenicidade , Encefalite de St. Louis/diagnóstico , Encefalite de St. Louis/epidemiologia , Humanos , Insetos Vetores , Meningite Asséptica/diagnóstico , Meningite Asséptica/epidemiologia , Prognóstico , América do Sul/epidemiologia , Estados Unidos/epidemiologiaRESUMO
St. Louis encephalitis virus infection was detected in summer 2015 in southern California after an 11-year absence, concomitant with an Arizona outbreak. Sequence comparisons showed close identity of California and Arizona isolates with 2005 Argentine isolates, suggesting introduction from South America and underscoring the value of continued arbovirus surveillance.
Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Vírus da Encefalite de St. Louis/genética , Encefalite de St. Louis/epidemiologia , Encefalite de St. Louis/virologia , Animais , California/epidemiologia , Doenças Transmissíveis Emergentes/história , Doenças Transmissíveis Emergentes/transmissão , Culicidae/virologia , Surtos de Doenças , Vírus da Encefalite de St. Louis/classificação , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/história , Encefalite de St. Louis/transmissão , Genes Virais , Genoma Viral , História do Século XXI , Humanos , Filogenia , Vigilância da População , Estações do AnoRESUMO
St. Louis encephalitis virus (SLEV) (Flavivirus) is a reemerging arbovirus in the southern cone of South America. In 2005, an outbreak of SLEV in central Argentina resulted in 47 human cases with 9 deaths. In Argentina, the ecology of SLEV is poorly understood. Because certain birds are the primary amplifiers in North America, we hypothesized that birds amplify SLEV in Argentina as well. We compared avian SLEV seroprevalence in a variety of ecosystems in and around Córdoba city from 2004 (before the epidemic) and 2005 (during the epidemic). We also explored spatial patterns to better understand the local ecology of SLEV transmission. Because West Nile virus (WNV) was also detected in Argentina in 2005, all analyses were also conducted for WNV. A total of 980 birds were sampled for detection of SLEV and WNV neutralizing antibodies. SLEV seroprevalence in birds increased 11-fold from 2004 to 2005. Our study demonstrated that a high proportion (99.3%) of local birds were susceptible to SLEV infection immediately prior to the 2005 outbreak, indicating that the vertebrate host population was primed to amplify SLEV. SLEV was found distributed in a variety of environments throughout the city of Córdoba. However, the force of viral transmission varied among sites. Fine scale differences in populations of vectors and vertebrate hosts would explain this variation. In summary, we showed that in 2005, both SLEV and to a lesser extent WNV circulated in the avian population. Eared Dove, Picui Ground-Dove and Great Kiskadee are strong candidates to amplify SLEV because of their exposure to the pathogen at the population level, and their widespread abundance. For the same reasons, Rufous Hornero may be an important maintenance host for WNV in central Argentina. Competence studies and vector feeding studies are needed to confirm these relationships.