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1.
EMBO Mol Med ; 12(11): e12628, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32945125

RESUMO

Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post-exposure prophylaxis (PEP), but it still causes about 60,000 deaths every year. No cure exists after the onset of clinical signs, and the case-fatality rate approaches 100% even with advanced supportive care. Here, we report that a combination of two potent neutralizing human monoclonal antibodies directed against the viral envelope glycoprotein cures symptomatic rabid mice. Treatment efficacy requires the concomitant administration of antibodies in the periphery and in the central nervous system through intracerebroventricular infusion. After such treatment, recovered mice presented good clinical condition, viral loads were undetectable, and the brain inflammatory profile was almost normal. Our findings provide the unprecedented proof of concept of an antibody-based therapeutic approach for symptomatic rabies.


Assuntos
Lyssavirus , Vacinas Antirrábicas , Vírus da Raiva , Raiva , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes , Anticorpos Antivirais , Cães , Humanos , Camundongos , Profilaxia Pós-Exposição , Raiva/tratamento farmacológico
2.
Emerg Microbes Infect ; 9(1): 851-854, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32403984

RESUMO

A second case of a novel rabies variant described once in a capuchin monkey from Mato Grosso, Brazil, was discovered in a rabid wild kinkajou from the same region, indicating a public health risk following exposure to either of the two animals.


Assuntos
Cebus/virologia , Procyonidae/virologia , Vírus da Raiva/isolamento & purificação , Raiva/transmissão , Animais , Brasil/epidemiologia , Genes Virais , Filogenia , Saúde Pública , Vírus da Raiva/genética
4.
Avian Pathol ; 46(5): 488-496, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28417679

RESUMO

Field observations indicate that the impact of velogenic Newcastle disease virus (vNDV) is more severe in countries with concomitant circulation of low pathogenicity avian influenza virus, as is the case in the Middle East, in particular in Israel, where H9N2 and NDV are endemic. In our study, we evaluated how the exposure of chickens to an H9N2 challenge either favours or interferes with a subsequent vNDV infection and its transmission to sentinels. For this purpose, single vNDV and sequential H9/NDV challenges were performed with increasing doses of vNDV (101-106 EID50). The H9N2 challenge made birds more susceptible to the vNDV, lowering the minimum dose required to cause an infection, exacerbating the clinical outcome, while delaying the onset of the disease and time of death. Interestingly, the presence and degree of these seemingly contrasting effects were dose-dependent and not mutually exclusive.


Assuntos
Galinhas , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária/virologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle , Doenças das Aves Domésticas/virologia , Animais , Anticorpos Antivirais , Coinfecção/veterinária , Organismos Livres de Patógenos Específicos
5.
EMBO Mol Med ; 8(4): 407-21, 2016 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-26992832

RESUMO

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Fatores Imunológicos/imunologia , Profilaxia Pós-Exposição/métodos , Vírus da Raiva/imunologia , Raiva/prevenção & controle , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/isolamento & purificação , Modelos Animais de Doenças , Humanos , Imunização Passiva/métodos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/isolamento & purificação , Mesocricetus , Análise de Sobrevida , Resultado do Tratamento
6.
Vet Res ; 46: 51, 2015 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-25963535

RESUMO

The study of influenza type A (IA) infections in wild mammals populations is a critical gap in our knowledge of how IA viruses evolve in novel hosts that could be in close contact with avian reservoir species and other wild animals. The aim of this study was to evaluate the susceptibility to infection, the nasal shedding and the transmissibility of the H7N1 and H5N1 highly pathogenic avian influenza (HPAI) viruses in the bank vole (Myodes glareolus), a wild rodent common throughout Europe and Asia. Two out of 24 H5N1-infected voles displayed evident respiratory distress, while H7N1-infected voles remained asymptomatic. Viable virus was isolated from nasal washes collected from animals infected with both HPAI viruses, and extra-pulmonary infection was confirmed in both experimental groups. Histopathological lesions were evident in the respiratory tract of infected animals, although immunohistochemistry positivity was only detected in lungs and trachea of two H7N1-infected voles. Both HPAI viruses were transmitted by direct contact, and seroconversion was confirmed in 50% and 12.5% of the asymptomatic sentinels in the H7N1 and H5N1 groups, respectively. Interestingly, viable virus was isolated from lungs and nasal washes collected from contact sentinels of both groups. The present study demonstrated that two non-rodent adapted HPAI viruses caused asymptomatic infection in bank voles, which shed high amounts of the viruses and were able to infect contact voles. Further investigations are needed to determine whether bank voles could be involved as silent hosts in the transmission of HPAI viruses to other mammals and domestic poultry.


Assuntos
Arvicolinae , Suscetibilidade a Doenças/veterinária , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus da Influenza A Subtipo H7N1/fisiologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Roedores/transmissão , Eliminação de Partículas Virais , Animais , Suscetibilidade a Doenças/virologia , Nariz/virologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Doenças dos Roedores/virologia
7.
Infect Genet Evol ; 17: 202-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23603764

RESUMO

Fox rabies re-emerged in north-eastern Italy at the end of 2008 and circulated until early 2011. As with previous rabies epidemics, the Italian cases were linked to the epidemiological situation in adjacent regions. To obtain a comprehensive picture of the dynamics of the recent Italian epidemic, we performed a detailed evolutionary analysis of RABVs circulating in north-eastern Italy. Sequences were obtained for the hyper-variable region of the nucleoprotein gene, the complete glycoprotein gene, and the intergenic region G-L from 113 selected fox rabies cases. We identified two viral genetic groups, here referred to as Italy-1 and Italy-2. Phylogenetic and phylogeographic analyses revealed that both groups had been circulating in the Western Balkans and Slovenia in previous years and were only later introduced into Italy (into the Friuli Venezia Giulia region-FVG), occupying different areas of the Italian territories. Notably, viruses belonging to the Italy-1 group remained confined to the region of introduction and their spread was minimised by the implementation of oral fox vaccination campaigns. In contrast, Italy-2 viruses spread westward over a territory of 100 km from their first identification in FVG, likely crossing the northern territories where surveillance was inadequate. A genetic sub-group (Italy-2A), characterised by a unique amino acid mutation (D106A) in the N gene, was also observed to occupy a distinct geographic cluster. This molecular epidemiological analysis of the 2008-2011 fox rabies epidemic will contribute to future control programmes both at national and regional levels. In particular, our findings highlight the weaknesses of the national surveillance strategy in the period preceding rabies re-emergence, and of control plans implemented immediately after rabies notification, and underline the need of a coordinated approach at the regional level for both the surveillance and control of wildlife rabies.


Assuntos
Raposas/virologia , Filogenia , Filogeografia , Vírus da Raiva/genética , Raiva/veterinária , Animais , Genes Virais , Itália/epidemiologia , Dados de Sequência Molecular , Vírus da Raiva/classificação , Vírus da Raiva/isolamento & purificação
8.
J Virol Methods ; 188(1-2): 13-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23178584

RESUMO

Newcastle Disease Virus (NDV) is the only member of serotype 1 avian paramyxoviruses (APMV-1) that causes respiratory and neurological disease in chickens and other species of birds and can cause severe economic losses in the poultry sector. Due to the relevant variability of the genome and the pathogenicity of NDV isolates, their detection in a specimen is not sufficient to provide and confirm an exact diagnosis, and so the assessment of virus pathotype is required. To diagnose rapidly and pathotype NDV directly in clinical specimens, a method based on RT-PCR and pyrosequencing analysis has been developed and is reported in the present study. A pair of degenerated primers was designed to amplify a portion of the fusion (F) gene responsible for virulence and used to test 315 specimens collected from 2006 to 2011. The subsequent pyrosequencing reaction identified a 30-bp region encompassing the cleavage site. A total of 213 out of 315 samples were pyrosequenced and results were compared and confirmed by the Sanger sequencing procedure, which is traditionally performed for NDV pathotyping. The pyrosequencing reaction provided high quality results in real time and proved to be more rapid and cost-efficient than the classical sequencing procedure, indicating it as a possible valid alternative to the currently used diagnostic assays for NDV.


Assuntos
Doenças das Aves/diagnóstico , Doenças das Aves/virologia , Vírus da Doença de Newcastle/classificação , Vírus da Doença de Newcastle/patogenicidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Análise de Sequência de DNA/métodos , Virologia/métodos , Animais , Aves , Vírus da Doença de Newcastle/genética
9.
J Clin Microbiol ; 49(5): 1932-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21389152

RESUMO

Rabies is a fatal zoonosis caused by a nonsegmented negative-strand RNA virus, namely, rabies virus (RABV). Apart from RABV, at least 10 additional species are known as rabies-related lyssaviruses (RRVs), and some of them are responsible for occasional spillovers into humans. More lyssaviruses have also been detected recently in different bat ecosystems, thanks to the application of molecular diagnostic methods. Due to the variety of the members of the genus Lyssavirus, there is the necessity to develop a reliable molecular assay for rabies diagnosis able to detect and differentiate among the existing rabies and rabies-related viruses. In the present study, a pyrosequencing protocol targeting the 3' terminus of the nucleoprotein (N) gene was applied for the rapid characterization of lyssaviruses. Correct identification of species was achieved for each sample tested. Results from the pyrosequencing assay were also confirmed by those obtained using the Sanger sequencing method. A pan-lyssavirus one-step reverse transcription (RT)-PCR was developed within the framework of the pyrosequencing procedure. The sensitivity (Se) of the one-step RT-PCR assay was determined by using in vitro-transcribed RNA and serial dilutions of titrated viruses. The assay demonstrated high analytical and relative specificity (Sp) (98.94%) and sensitivity (99.71%). To date, this is the first case in which pyrosequencing has been applied for lyssavirus identification using a cheaper diagnostic approach than the one for all the other protocols for rapid typing that we are acquainted with. Results from this study indicate that this procedure is suitable for lyssavirus detection in samples of both human and animal origin.


Assuntos
Vírus da Raiva/classificação , Vírus da Raiva/isolamento & purificação , Raiva/diagnóstico , Raiva/veterinária , Análise de Sequência de DNA/métodos , Virologia/métodos , Animais , Humanos , Nucleoproteínas/genética , RNA Viral/genética , Raiva/virologia , Vírus da Raiva/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade , Proteínas Virais/genética
10.
Vet Res ; 41(5): 66, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20546698

RESUMO

Highly pathogenic avian influenza (HPAI) viruses of the H5 and H7 subtype pose a major public health threat due to their capacity to cross the species barrier and infect mammals, for example dogs, cats and humans. In the present study we tested the capacity of selected H7 and H5 HPAI viruses to infect and to be transmitted from infected BALB/c mice to contact sentinels. Previous experiments have shown that viruses belonging to both H5 and H7 subtypes replicate in the respiratory tract and central nervous system of experimentally infected mice. In this study we show that selected H7N1 and H5N1 HPAI viruses can be transmitted from mouse-to-mouse by direct contact, and that in experimentally infected animals they exhibit a different pattern of replication and transmission. Our results can be considered as a starting point for transmission experiments involving other influenza A viruses with alpha 2-3 receptor affinity in order to better understand the viral factors influencing transmissibility of these viruses in selected mammalian species.


Assuntos
Virus da Influenza A Subtipo H5N1/patogenicidade , Vírus da Influenza A Subtipo H7N1/patogenicidade , Infecções por Orthomyxoviridae/virologia , Animais , Feminino , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus da Influenza A Subtipo H7N1/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Nariz/virologia , Fatores de Tempo , Eliminação de Partículas Virais
11.
J Clin Microbiol ; 46(5): 1769-73, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18367569

RESUMO

Among the different hemagglutinin (HA) subtypes of avian influenza (AI) viruses, H5, H7, and H9 are of major interest because of the serious consequences for the poultry industry and the increasing frequency of direct transmission of these viruses to humans. The availability of new tools to rapidly detect and subtype the influenza viruses can enable the immediate application of measures to prevent the widespread transmission of the infection. In this study, a novel one-step real-time reverse transcription-PCR (RRT-PCR) was developed to detect simultaneously the H5, H7, and H9 subtypes of AI viruses from clinical samples of avian origin. The sensitivity of the RRT-PCR assay was determined by using in vitro-transcribed RNA and 10-fold serial dilutions of titrated AI viruses. High sensitivity levels were obtained, with limits of detection ranging from 10(1) to 10(3) RNA copies and from 10(1) 50% egg infectious dose (EID(50))/100 microl to 10(2.74) EID(50)/100 microl with titrated viruses. Excellent results were achieved in the intra- and interassay variability tests. The comparison of the results with those obtained from the analysis of 725 avian samples by means of the reference method (virus isolation [VI]) showed a high level of agreement. To date, this is the first real-time PCR protocol available for the simultaneous detection of AI viruses belonging to subtypes H5, H7, and H9, and the results obtained indicate that this method is suitable as a routine laboratory test for the rapid detection and differentiation of the three most-important AI virus subtypes in samples of avian origin.


Assuntos
Influenza Aviária/virologia , Orthomyxoviridae/classificação , Orthomyxoviridae/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Animais , Aves , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Orthomyxoviridae/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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