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1.
Orv Hetil ; 160(51): 2026-2035, 2019 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-31838862

RESUMO

Introduction: According to the European Centre for Disease Prevention and Control, the prevalence of neuroinvasive symptoms caused by the West Nile virus (WNV) has significantly increased in the past years throughout Europe, including Hungary. The rise may be attributed to changes in precipitation and climate. The WNV zoonosis is spread by mosquitoes. It is mostly asymptomatic, flu-like symptoms occur in 20% of the cases and in less than 1% a neuroinvasive disease with a lethal outcome may develop. Aim: Our aim was to demonstrate the neuroinvasive symptomatology and the diagnosis and treatment of WNV infections by describing our patient cases as well as to resolve differential diagnostic dilemmas. Method: We report the cases of 4 patients treated at the "Moritz Kaposi" Somogy County Hospital between the 31st July and 4th September, 2018, with WNV, whose diagnoses were confirmed by serological and molecular biological methods. An epidemiological overview of WNV infections was also given. Results: Four patients were confirmed to have had WNV infection in the given time period. A wide range of neurological symptoms were observed in each patient and death occurred in one case. The patients were elderly with a number of comorbidities. Conclusions: The appearance of more severe, neuroinvasive symptoms following WNV infections is also characteristic of Hungary. The treatment of the infection is supportive, including giving pain relievers and the management of secondary infections. It is important to consider the possibility of a WNV infection in the case of a neurological disease of unknown origin, particularly if the symptoms indicate encephalitis. Orv Hetil. 2019; 160(51): 2026-2035.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Encefalite Viral/epidemiologia , Febre do Nilo Ocidental/diagnóstico , Vírus do Nilo Ocidental/isolamento & purificação , Idoso , Animais , Anticorpos Antivirais/sangue , Humanos , Hungria/epidemiologia , Prevalência , Febre do Nilo Ocidental/epidemiologia
2.
BMC Infect Dis ; 19(1): 912, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664929

RESUMO

BACKGROUND: West Nile virus (WNV) circulates across Australia and was referred to historically as Kunjin virus (WNVKUN). WNVKUN has been considered more benign than other WNV strains circulating globally. In 2011, a more virulent form of the virus emerged during an outbreak of equine arboviral disease in Australia. METHODS: To better understand the emergence of this virulent phenotype and the mechanism by which pathogenicity is manifested in its host, cells were infected with either the virulent strain (NSW2012), or less pathogenic historical isolates, and their innate immune responses compared by digital immune gene expression profiling. Two different cell systems were used: a neuroblastoma cell line (SK-N-SH cells) and neuronal cells derived from induced pluripotent stem cells (iPSCs). RESULTS: Significant innate immune gene induction was observed in both systems. The NSW2012 isolate induced higher gene expression of two genes (IL-8 and CCL2) when compared with cells infected with less pathogenic isolates. Pathway analysis of induced inflammation-associated genes also indicated generally higher activation in infected NSW2012 cells. However, this differential response was not paralleled in the neuronal cultures. CONCLUSION: NSW2012 may have unique genetic characteristics which contributed to the outbreak. The data herein is consistent with the possibility that the virulence of NSW2012 is underpinned by increased induction of inflammatory genes.


Assuntos
Surtos de Doenças , Imunidade Inata/genética , Inflamação/genética , Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental/genética , Austrália/epidemiologia , Linhagem Celular Tumoral , Quimiocina CCL2/genética , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Interleucina-8/genética , Neurônios/virologia , Fenótipo , Virulência , Vírus do Nilo Ocidental/patogenicidade
4.
PLoS Pathog ; 15(8): e1007899, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31415679

RESUMO

West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. We evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. When challenged with WNV, STING knock out (-/-) mice displayed increased morbidity and mortality compared to wild type (WT) mice. Virologic analysis and assessment of STING activation revealed that STING signaling was not required for control of WNV in the spleen nor was WNV sufficient to mediate canonical STING activation in vitro. However, STING-/- mice exhibited a clear trend of increased viral load and virus dissemination in the CNS. We found that STING-/- mice exhibited increased and prolonged neurological signs compared to WT mice. Pathological examination revealed increased lesions, mononuclear cellular infiltration and neuronal death in the CNS of STING-/- mice, with sustained pathology after viral clearance. We found that STING was required in bone marrow derived macrophages for early control of WNV replication and innate immune activation. In vivo, STING-/- mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. Our findings demonstrate that STING plays a critical role in immune programming for the control of neurotropic WNV infection and CNS disease.


Assuntos
Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Imunidade Inata/imunologia , Proteínas de Membrana/fisiologia , Replicação Viral , Febre do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/imunologia , Animais , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/virologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Carga Viral , Febre do Nilo Ocidental/metabolismo , Febre do Nilo Ocidental/virologia
5.
Nat Commun ; 10(1): 3649, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409781

RESUMO

RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. Here, we use a systems biology approach to define the contributions of each RLR in the innate immune response to WNV. Genome-wide RNAseq and bioinformatics analyses of macrophages from mice lacking either RLR reveal that the RLRs drive distinct immune gene activation and response polarization to mediate an M1/inflammatory signature while suppressing the M2/wound healing phenotype. While LGP2 functions to modulate inflammatory signaling, RIG-I and MDA5 together are essential for M1 macrophage polarization in vivo and the control of WNV infection through potential downstream control of ATF4 and SMAD4 to regulate target gene expression for cell polarization. These analyses reveal the RLR-driven signature of macrophage polarization, innate immune protection, and immune programming against WNV infection.


Assuntos
Proteína DEAD-box 58/imunologia , Macrófagos/imunologia , Febre do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/fisiologia , Animais , Polaridade Celular , Proteína DEAD-box 58/genética , Feminino , Humanos , Helicase IFIH1 Induzida por Interferon/genética , Helicase IFIH1 Induzida por Interferon/imunologia , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Febre do Nilo Ocidental/genética , Febre do Nilo Ocidental/fisiopatologia , Febre do Nilo Ocidental/virologia
6.
MMWR Morb Mortal Wkly Rep ; 68(31): 673-678, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31393865

RESUMO

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including eastern equine encephalitis, Jamestown Canyon, La Crosse, Powassan, and St. Louis encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC for 2018 on nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because they are primarily nondomestic viruses typically acquired through travel. In 2018, 48 states and the District of Columbia (DC) reported 2,813 cases of domestic arboviral disease, including 2,647 (94%) WNV disease cases. Of the WNV disease cases, 1,658 (63%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, and acute flaccid paralysis), for a national incidence of 0.51 cases of WNV neuroinvasive disease per 100,000 population. Because arboviral diseases continue to cause serious illness and have no definitive treatment, maintaining surveillance is important to direct and promote prevention activities. Health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis, perform appropriate diagnostic testing, and report cases to public health authorities.


Assuntos
Infecções por Arbovirus/epidemiologia , Surtos de Doenças , Vigilância da População , Febre do Nilo Ocidental/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Notificação de Doenças , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
7.
Parasit Vectors ; 12(1): 395, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395085

RESUMO

BACKGROUND: West Nile virus (WNV) is a mosquito-transmitted disease of birds that has caused bird population declines and can spill over into human populations. Previous research has identified bird species that infect a large fraction of the total pool of infected mosquitoes and correlate with human infection risk; however, these analyses cover small spatial regions and cannot be used to predict transmission in bird communities in which these species are rare or absent. Here we present a mechanistic model for WNV transmission that predicts WNV spread (R0) in any bird community in North America by scaling up from the physiological responses of individual birds to transmission at the level of the community. We predict unmeasured bird species' responses to infection using phylogenetic imputation, based on these species' phylogenetic relationships with bird species with measured responses. RESULTS: We focused our analysis on Texas, USA, because it is among the states with the highest total incidence of WNV in humans and is well sampled by birders in the eBird database. Spatio-temporal patterns: WNV transmission is primarily driven by temperature variation across time and space, and secondarily by bird community composition. In Texas, we predicted WNV R0 to be highest in the spring and fall when temperatures maximize the product of mosquito transmission and survival probabilities. In the most favorable months for WNV transmission (April, May, September and October), we predicted R0 to be highest in the "Piney Woods" and "Oak Woods & Prairies" ecoregions of Texas, and lowest in the "High Plains" and "South Texas Brush County" ecoregions. Dilution effect: More abundant bird species are more competent hosts for WNV, and predicted WNV R0 decreases with increasing species richness. Keystone species: We predicted that northern cardinals (Cardinalis cardinalis) are the most important hosts for amplifying WNV and that mourning doves (Zenaida macroura) are the most important sinks of infection across Texas. CONCLUSIONS: Despite some data limitations, we demonstrate the power of phylogenetic imputation in predicting disease transmission in heterogeneous host communities. Our mechanistic modeling framework shows promise both for assisting future analyses on transmission and spillover in heterogeneous multispecies pathogen systems and for improving model transparency by clarifying assumptions, choices and shortcomings in complex ecological analyses.


Assuntos
Doenças das Aves/transmissão , Aves/virologia , Culicidae/virologia , Modelos Biológicos , Febre do Nilo Ocidental/veterinária , Animais , Doenças das Aves/virologia , América do Norte/epidemiologia , Filogenia , Estações do Ano , Texas/epidemiologia , Febre do Nilo Ocidental/transmissão , Vírus do Nilo Ocidental/fisiologia
8.
PLoS Negl Trop Dis ; 13(8): e0007649, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31442225

RESUMO

The explosive spread of Zika virus (ZIKV) and associated complications in flavivirus-endemic regions underscore the need for sensitive and specific serodiagnostic tests to distinguish ZIKV, dengue virus (DENV) and other flavivirus infections. Compared with traditional envelope protein-based assays, several nonstructural protein 1 (NS1)-based assays showed improved specificity, however, none can detect and discriminate three flaviviruses in a single assay. Moreover, secondary DENV infection and ZIKV infection with previous DENV infection, both common in endemic regions, cannot be discriminated. In this study, we developed a high-throughput and multiplex IgG microsphere immunoassay (MIA) using the NS1 proteins of DENV1-DENV4, ZIKV and West Nile virus (WNV) to test samples from reverse-transcription-polymerase-chain reaction-confirmed cases, including primary DENV1, DENV2, DENV3, WNV and ZIKV infections, secondary DENV infection, and ZIKV infection with previous DENV infection. Combination of four DENV NS1 IgG MIAs revealed a sensitivity of 94.3% and specificity of 97.2% to detect DENV infection. The ZIKV and WNV NS1 IgG MIAs had a sensitivity/specificity of 100%/87.9% and 86.1%/78.4%, respectively. A positive correlation was found between the readouts of enzyme-linked immunosorbent assay and MIA for different NS1 tested. Based on the ratio of relative median fluorescence intensity of ZIKV NS1 to DENV1 NS1, the IgG MIA can distinguish ZIKV infection with previous DENV infection and secondary DENV infection with a sensitivity of 88.9-90.0% and specificity of 91.7-100.0%. The multiplex and high-throughput assay could be applied to serodiagnosis and serosurveillance of DENV, ZIKV and WNV infections in endemic regions.


Assuntos
Anticorpos Antivirais/sangue , Dengue/diagnóstico , Imunoensaio/métodos , Microesferas , Testes Sorológicos/métodos , Febre do Nilo Ocidental/diagnóstico , Infecção por Zika virus/diagnóstico , Ensaios de Triagem em Larga Escala , Humanos , Imunoglobulina G/sangue , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
9.
Nat Commun ; 10(1): 3889, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467282

RESUMO

The innate response to a pathogen is critical in determining the outcome of the infection. However, the interplay of different cellular responses that are activated following viral infection and their contribution to innate antiviral signalling has not been clearly established. This work shows that flaviviruses, including Dengue, Zika, West Nile and Tick-borne encephalitis viruses, activate the unfolded protein response before transcription of interferon regulatory factor 3 induced genes. Infection in conditions of unfolded protein response priming leads to early activation of innate antiviral responses and cell intrinsic inhibition of viral replication, which is interferon regulatory factor 3 dependent. These results demonstrate that the unfolded protein response is not only a physiological reaction of the cell to viral infection, but also synergizes with pattern recognition sensing to mount a potent antiviral response.


Assuntos
Antivirais/farmacologia , Infecções por Flavivirus/imunologia , Interações Hospedeiro-Patógeno/fisiologia , Imunidade Inata/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Animais , Proteína DEAD-box 58/metabolismo , Dengue/imunologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Encefalite Transmitidos por Carrapatos/efeitos dos fármacos , Encefalite Transmitida por Carrapatos/imunologia , Endorribonucleases/metabolismo , Feminino , Humanos , Fator Regulador 3 de Interferon/metabolismo , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Transcriptoma , Células Vero , Replicação Viral/efeitos dos fármacos , Febre do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Infecção por Zika virus/imunologia
10.
Ann Otol Rhinol Laryngol ; 128(12): 1198-1202, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31366220

RESUMO

OBJECTIVES: West Nile virus (WNV) has been spreading over the last 20 years. Human infection is asymptomatic in most cases. When the disease becomes clinically manifest, it may involve a range of issues, from a mild infection with flu-like symptoms to a neuroinvasive disease. Albeit rarely, WNV-associated sensorineural hearing loss (SNHL) has also been reported. Here we describe two new cases of SNHL and balance impairment caused by WNV infection. METHODS: The patients were investigated with repeated audiometric tests and, for the first time, videonystagmography was also used. RESULTS: Unlike findings in the few other published cases, an improvement in audiometric thresholds and vestibular function was documented in both of our patients. CONCLUSIONS: In the light of our findings, a prospective study would be warranted on a large series of patients with WNV infection in order: (i) to better define the epidemiology of the related cochlear-vestibular involvement; and (ii) to elucidate the virus-related changes to peripheral and central auditory and vestibular functions.


Assuntos
Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/virologia , Febre do Nilo Ocidental/complicações , Idoso , Perda Auditiva Neurossensorial/terapia , Humanos , Masculino , Pessoa de Meia-Idade
11.
BMJ Case Rep ; 12(7)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31345830

RESUMO

A man in his 70s with known systemic lupus erythematosus (SLE) was admitted with confusion, worsening proteinuria and cutaneous vasculitis despite adherence to his home immunosuppressive regimen. Admission laboratories were consistent with active lupus. Despite treatment with pulse-dose glucocorticoids and intravenous immunoglobulin, he developed worsening mental status and meningeal signs. Investigations revealed cerebrospinal fluid (CSF) neutrophilic and plasmacytic pleocytosis and negative cultures. Empiric treatment for SLE flare with potential neuropsychiatric involvement was continued while workup for altered mental status was ongoing. Ultimately, West Nile encephalitis was diagnosed by CSF serologies, and steroids were tapered. Altered mental status in a patient with SLE has a broad differential, and primary neuropsychiatric SLE should be considered only after exclusion of secondary causes. Although evidence of end-organ SLE activity usually lends support to a neuropsychiatric SLE diagnosis, in this case, serological and clinical evidence of SLE activity may have been triggered by acute viral infection.


Assuntos
Confusão/virologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/virologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Proteinúria/virologia , Febre do Nilo Ocidental/diagnóstico , Vírus do Nilo Ocidental/isolamento & purificação , Idoso , Diagnóstico Diferencial , Eletroencefalografia , Evolução Fatal , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Punção Espinal , Febre do Nilo Ocidental/fisiopatologia , Febre do Nilo Ocidental/terapia
12.
Prev Vet Med ; 169: 104706, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31311639

RESUMO

The international nature of the equine industry provides opportunities for the spread of infectious diseases between countries. While incursions of exotic diseases into the United Kingdom (UK) equine population have been rare, the potential socioeconomic and welfare impacts are a significant concern. However, little is known about leisure horse owners' ability or willingness to prepare for an exotic disease incursion. The objectives of this study were to describe UK leisure horse owners' awareness and perceptions of exotic diseases, and to identify clusters of horse owners characterised by their awareness and perceived risk of exotic diseases. A cross-sectional study of leisure horse owners in the UK was conducted between April and July 2018. Participants (n = 403) completed an online questionnaire with questions pertaining to demographics, experiences with endemic diseases, and awareness and perceptions of exotic diseases. Hierarchical cluster analysis was used to identify groups of participants that were similar in regard to their awareness and perceived risk of exotic diseases. Participants identified a median of 3 (IQR 2-4) exotic diseases, with the most recognised exotic diseases being African horse sickness and West Nile virus. The most frequently mentioned clinical signs that participants thought were associated with exotic diseases included high temperature (57.2%), discharge (46.5%), and lack of energy (41.2%). Hierarchical cluster analysis identified three clusters of participants: 1) those who were aware of exotic diseases and perceived a high amount of risk (n = 78); 2) those who were aware of exotic diseases but perceived a low amount of risk (n = 111); and 3) those who were less aware of exotic diseases and perceived a low amount of risk (n = 214). Efforts to communicate the relevance and consequences of exotic diseases to horse owners should consider the potential difference in receptiveness among horse owners in each cluster. Further investigations are required to determine the implications of horse owners' perceived risk on exotic disease preparedness.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Doenças dos Cavalos/psicologia , Adolescente , Adulto , Doença Equina Africana/psicologia , Criação de Animais Domésticos , Animais , Análise por Conglomerados , Estudos Transversais , Análise Fatorial , Feminino , Cavalos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Reino Unido , Febre do Nilo Ocidental/psicologia , Vírus do Nilo Ocidental , Adulto Jovem
13.
PLoS Negl Trop Dis ; 13(7): e0007473, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31306420

RESUMO

The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence. Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before. In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses. These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus. The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro. Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status. In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes. Only NYP showed reduced vector competence in both Cx. quinquefasciatus and Cx. tarsalis. Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants. These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.


Assuntos
Vetores de Doenças , Proteínas do Envelope Viral/metabolismo , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/metabolismo , Aedes , Motivos de Aminoácidos , Animais , Culex/virologia , Culicidae/virologia , Modelos Animais de Doenças , Feminino , Glicosilação , Concentração de Íons de Hidrogênio , Camundongos , Mutação , Fenótipo , Pardais/virologia , Células Vero , Proteínas do Envelope Viral/genética , Viremia , Virulência , Replicação Viral , Vírus do Nilo Ocidental/genética
17.
Transbound Emerg Dis ; 66(5): 2100-2106, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150146

RESUMO

This study aims at assessing the serological cross-reactions existing between three mosquito-borne flaviviruses with avian reservoirs co-circulating in Europe: West Nile (WNV), Usutu (USUV) and Bagaza (BAGV). The study is useful for a better interpretation of serological results in diagnostics and surveillance. Serum samples obtained from a natural host, the red-legged partridge (Alectoris rufa), experimentally infected with WNV, USUV or BAGV were analysed using two commercially available WNV competition ELISAs suitable for serological surveillance, and by the confirmatory virus neutralization test (VNT). The ELISAs examined showed different levels of specificity for WNV, as judged by cross-reaction observed with the other flaviviruses. By VNT, virus-specific antibodies were confirmed in 80%, 50% or 0% of sera from WNV-, BAGV-, or USUV-inoculated birds, respectively. The results indicate how the co-circulation of cross-reacting flaviviruses may affect the outcomes of WNV serological surveillance when applying currently available serological tools. On the one hand, the choice of the ELISA test for antibody screening should consider the differences found in specificity, since one test is more specific for WNV while the other one is more suitable for detection of a broader range of flavivirus antibodies. On the other hand, besides corroborating that cross-neutralization occurs between flaviviruses from different serocomplexes (WNV/USUV and BAGV), this study points out that cross-neutralization between WNV and USUV is not symmetric, and reveals the difficulty to identify USUV infections serologically. This finding indicates that actual USUV infections might be underestimated in the current diagnostic schemes.


Assuntos
Infecções por Flavivirus/veterinária , Flavivirus/isolamento & purificação , Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental/isolamento & purificação , Animais , Anticorpos Antivirais/sangue , Aves/virologia , Reações Cruzadas , Culicidae/virologia , Ensaio de Imunoadsorção Enzimática/veterinária , Monitoramento Epidemiológico , Europa (Continente)
18.
Nat Neurosci ; 22(8): 1276-1288, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31235930

RESUMO

T cells clear virus from the CNS and dynamically regulate brain functions, including spatial learning, through cytokine signaling. Here we determined whether hippocampal T cells that persist after recovery from infection with West Nile virus (WNV) or Zika virus (ZIKV) impact hippocampal-dependent learning and memory. Using newly established models of viral encephalitis recovery in adult animals, we show that in mice that have recovered from WNV or ZIKV infection, T cell-derived interferon-γ (IFN-γ) signaling in microglia underlies spatial-learning defects via virus-target-specific mechanisms. Following recovery from WNV infection, mice showed presynaptic termini elimination with lack of repair, while for ZIKV, mice showed extensive neuronal apoptosis with loss of postsynaptic termini. Accordingly, animals deficient in CD8+ T cells or IFN-γ signaling in microglia demonstrated protection against synapse elimination following WNV infection and decreased neuronal apoptosis with synapse recovery following ZIKV infection. Thus, T cell signaling to microglia drives post-infectious cognitive sequelae that are associated with emerging neurotropic flaviviruses.


Assuntos
Transtornos Cognitivos/psicologia , Infecções por Flavivirus/imunologia , Infecções por Flavivirus/psicologia , Microglia/imunologia , Sinapses/imunologia , Sinapses/patologia , Linfócitos T/imunologia , Animais , Apoptose , Linfócitos T CD8-Positivos/imunologia , Transtornos Cognitivos/etiologia , Feminino , Infecções por Flavivirus/patologia , Interferon gama , /psicologia , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Interferon/genética , Febre do Nilo Ocidental/imunologia , Febre do Nilo Ocidental/psicologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/psicologia
19.
PLoS Negl Trop Dis ; 13(5): e0007334, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31059502

RESUMO

BACKGROUND: The recent reports of Aedes aegypti and Ae. albopictus populations in Turkey, in parallel with the territorial expansion identified in several surrounding countries, have raised concerns about the establishment and re-establishment of these invasive Aedes mosquitoes in Turkey. This cross-sectional study was performed to detect Aedes aegypti and Ae. albopictus in regions of recent incursions, and screen for viral pathogens known to be transmitted elsewhere by these species. METHODOLOGY: Mosquitoes were collected at several locations in Artvin, Rize and Trabzon provinces of the Black Sea region during 2016-2017, identified morphologically, pooled and analyzed via generic or specific nucleic acid amplification assays. Viruses in positive pools were identified by product sequencing, cell culture inoculation and next generation sequencing (NGS) in selected specimens. PRINCIPAL FINDINGS: The study group comprised 791 specimens. Aedes albopictus was the most abundant species in all locations (89.6%), followed by Ae. aegypti (7.8%) and Culex pipiens (2.5%). Mosquitoes were screened for viruses in 65 pools where fifteen (23.1%) were reactive. The infecting strains was identified as West Nile virus (WNV) in 5 pools (7.7%) with Ae. albopictus or Cx. pipiens mosquitoes. The obtained WNV sequences phylogenetically grouped with local and global lineage 1 clade 1a viruses. In 4 (6.2%) and 6 (9.2%) pools, respectively, cell fusing agent virus (CFAV) and Aedes flavivirus (AEFV) sequences were characterized. NGS provided a near-complete AEFV genome in a pool of Ae. albopictus. The strain is provisionally called "AEFV-Turkey", and functional analysis of the genome revealed several conserved motifs and regions associated with virus replication. Merida-like virus Turkey (MERDLVT), a recently-described novel rhabdovirus, was also co-detected in a Cx. pipiens pool also positive for WNV. CONCLUSIONS/SIGNIFICANCE: Invasive Aedes mosquitoes are established in certain locations of northeastern Turkey. Herein we conclusively show the role of these species in WNV circulation in the region. Biosurveillance is imperative to monitor the spread of these species further into Asia Minor and to detect possible introduction of pathogens.


Assuntos
Aedes/virologia , Mosquitos Vetores/virologia , Febre do Nilo Ocidental/transmissão , Vírus do Nilo Ocidental/isolamento & purificação , Aedes/classificação , Animais , Estudos Transversais , Feminino , Flavivirus/classificação , Flavivirus/genética , Flavivirus/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mosquitos Vetores/classificação , Filogenia , Especificidade da Espécie , Turquia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/classificação , Vírus do Nilo Ocidental/genética
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