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1.
Fish Shellfish Immunol ; 92: 736-745, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284045

RESUMO

Viral diseases in aquaculture were challenging because there are few preventative measures and/or treatments. Our previous study indicated that imidazole arctigenin derivatives possessed antiviral activities against infectious hematopoietic necrosis virus (IHNV). Based on the structure-activity relationship in that study, a new imidazole arctigenin derivative, 4-(8-(2-ethylimidazole)octyloxy)-arctigenin (EOA), was designed, synthesized and its anti-IHNV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC50), we found that EOA (IC50 = 0.56 mg/L) possessed a higher antiviral activity than those imidazole arctigenin derivatives in our previous study. Besides, EOA could significantly decrease cytopathic effect (CPE) and viral titer induced by IHNV in epithelioma papulosum cyprinid (EPC) cells. In addition, EOA significantly inhibited apoptosis induced by IHNV in EPC cells. Further data verified that EOA inhibited IHNV replication in rainbow trout, with reducing 32.0% mortality of IHNV-infected fish. The results suggested that EOA was more stable with a prolonged inhibitory half-life in the early stage of virus infection (1-4 days). Consistent with above results, EOA repressed IHNV glycoprotein gene expression in virus sensitive tissues (kidney and spleen) in the early stage of virus infection. Moreover, histopathological evaluation showed that tissues from the spleen and kidney of fish infected with IHNV exhibited pathological changes. But there were no lesions in any of the tissues from the control group and EOA-treaten group. In accordance with the histopathological assay, EOA could elicited anti-inflammation response in non-viral infected rainbow trout by down-regulating the expression of cytokine genes (IL-8, IL-12p40, and TNF-α). Altogether, EOA was expected to be a therapeutic agent against IHNV infection in the field of aquaculture.


Assuntos
Antivirais/farmacologia , Doenças dos Peixes/prevenção & controle , Furanos/farmacologia , Vírus da Necrose Hematopoética Infecciosa/efeitos dos fármacos , Lignanas/farmacologia , Oncorhynchus mykiss , Animais , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos/veterinária , Doenças dos Peixes/virologia , Testes de Sensibilidade Microbiana/veterinária , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/veterinária , Infecções por Rhabdoviridae/virologia
2.
Fish Shellfish Immunol ; 89: 537-547, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30991145

RESUMO

Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide. The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV. Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity. In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A. Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation. Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication. Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days. This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape. In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.


Assuntos
Doenças dos Peixes/prevenção & controle , Glicoproteínas/imunologia , Vírus da Necrose Hematopoética Infecciosa/imunologia , Vírus da Necrose Hematopoética Infecciosa/patogenicidade , Oncorhynchus mykiss , Infecções por Rhabdoviridae/veterinária , Vacinas Virais/imunologia , Animais , Doenças dos Peixes/imunologia , Glicosilação , Imunogenicidade da Vacina/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Virulência
3.
Fish Shellfish Immunol ; 89: 516-524, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30986537

RESUMO

Infectious hematopoietic necrosis virus (IHNV) leads to serious disease and economic losses in the salmonid aquaculture industry. The present study aimed to develop an effective and efficient vaccine to protect rainbow trout (Oncorhynchus mykiss) against IHNV infection. Administered via the immersion route, a live vector vaccine containing the regions of the IHNV glycoprotein (G) induced immune responses in rainbow trout. Use of the immersion route induced more-efficient mucosal immunity than intramuscular injection vaccination. IHNV G gene expression was detected in the spleens of rainbow trout at 3, 7 and 15 days post-vaccination (dpv). The G gene expression continuously decreased between 3 and 15 dpv. In addition, the expression of TLR-3, TLR-7 and TLR-8 was upregulated after vaccination, and the highest expression levels of IFN-1, Mx-1, Mx-3, Vig-1 and Vig-2 were observed at 3 dpv. Four markers of the adaptive immune response (CD4, CD8, IgM and IgT) gradually increased. When experimental fish were challenged with IHNV by immersion, significant differences in cumulative percentage mortality were observed in the vaccinated fish and the unvaccinated (empty-plasmid-vaccinated) fish. The relative survival rate was 92% and 6% in the vaccinated group and empty-plasmid group, respectively. Serum antibody levels gradually increased in the vaccinated fish, unlike in the unvaccinated fish, after 7 dpv. Our results suggest there was a significant increase in fish immune responses and resistance to infection with IHNV following administration of the live vector vaccine. Therefore, this live vector vaccine is a promising vaccine that may be utilized to protect rainbow trout against IHNV.


Assuntos
Imunidade Adaptativa , Doenças dos Peixes/prevenção & controle , Vírus da Necrose Hematopoética Infecciosa/fisiologia , Oncorhynchus mykiss , Infecções por Rhabdoviridae/veterinária , Vacinas Virais/imunologia , Animais , Doenças dos Peixes/imunologia , Glicoproteínas/genética , Glicoproteínas/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Baço/imunologia , Vacinas Atenuadas/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia
4.
Fish Shellfish Immunol ; 88: 403-406, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30862516

RESUMO

IFN-γ is a pleiotropic cytokine with significant roles in antiviral, antitumor and immune regulation. It could be used as an immuno-enhancer to improve fish protectiveness against pathogens. In this study, the prokaryotic expression plasmid pTwin1-N-IFN-γ was constructed to express Cyprinus carpio (common carp) IFN-γ fused with a chitin binding domain (CBD) and a self-cleavable intein-tag, Synechocystis sp DnaB. The recombinant protein CBD-DnaB-IFN-γ with the molecular weight of 44.25 kD was successfully expressed in soluble form, and the rIFN-γ (approximate 18.61 kD) was further cleaved and eluted under pH = 7.0 at 25 °C. rIFN-γ could be recognized by western blotting with rabbit anti-grass carp IFN-γ polyclonal antibody. Cytotoxicity studies on EPC cells showed that only 500 ng/ml rIFN-γ had a subtle effect on cells growth and its proliferation rate was reduced to 76.2%. EPC cells incubated with 100 ng/ml rIFN-γ showed significantly higher resistance against SVCV, reducing the TCID50/ml by more than 800-fold. In vivo studies suggested that intraperitoneal injection of rIFN-γ significantly improved the survival rate of common carps compared with SVCV challenge alone. These results implied that rIFN-γ would act as an immuno-enhancer in carp aquaculture.


Assuntos
Carpas/virologia , Doenças dos Peixes/prevenção & controle , Inteínas/genética , Interferon gama/imunologia , Infecções por Rhabdoviridae/veterinária , Animais , Aquicultura , Carpas/imunologia , Linhagem Celular Tumoral , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Imunidade Inata , Interferon gama/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Viremia/imunologia
5.
J Fish Dis ; 42(5): 631-642, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30874325

RESUMO

Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are important pathogens in rainbow trout farming worldwide. Their co-infection is also common, which causes great economic loss in juvenile salmon species. Development of a universal virus vaccine providing broadly cross-protective immunity will be of great importance. In this study, we generated two recombinant (r) virus (rIHNV-N438A-ΔNV-EGFP and rIHNV-N438A-ΔNV-VP2) replacing the NV gene of the backbone of rIHNV at the single point mutation at residue 438 with an efficient green fluorescent protein (EGFP) reporter gene and antigenic VP2 gene of IPNV. Meanwhile, we tested their efficacy against the wild-type (wt) IHNV HLJ-09 virus and IPNV serotype Sp virus challenge. The relative per cent survival rates of two recombinant viruses against (wt) IHNV HLJ-09 virus challenge were 84.6% and 81.5%, respectively. Simultaneously, the relative per cent survival rate of rIHNV-N438A-ΔNV-VP2 against IPNV serotype Sp virus challenge was 88.9%. It showed the two recombinant viruses had high protection rates and induced a high level of antibodies against IHNV or IPNV. Taken together, these results suggest the VP2 gene of IPNV can act as candidate gene for vaccine and attenuated multivalent live vaccines and molecular marker vaccines have potential application for viral vaccine.


Assuntos
Imunidade Adaptativa , Doenças dos Peixes/prevenção & controle , Vírus da Necrose Hematopoética Infecciosa/imunologia , Vírus da Necrose Pancreática Infecciosa/imunologia , Oncorhynchus mykiss , Vacinas Virais/imunologia , Animais , Infecções por Birnaviridae/imunologia , Infecções por Birnaviridae/prevenção & controle , Infecções por Birnaviridae/veterinária , Doenças dos Peixes/imunologia , Vírus da Necrose Hematopoética Infecciosa/genética , Vírus da Necrose Pancreática Infecciosa/genética , Distribuição Aleatória , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/veterinária , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
6.
Fish Shellfish Immunol ; 85: 66-77, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29567136

RESUMO

We recently reported on a successful vaccine for carp against SVCV based on the intramuscular injection of a DNA plasmid encoding the SVCV glycoprotein (SVCV-G). This shows that the intramuscular (i.m.) route of vaccination is suitable to trigger protective responses against SVCV, and that the SVCV G-protein is a suitable vaccine antigen. Yet, despite the general success of DNA vaccines, especially against fish rhabdoviruses, their practical implementation still faces legislative as well as consumer's acceptance concerns. Furthermore, the i.m. route of plasmid administration is not easily combined with most of the current vaccination regimes largely based on intraperitoneal or immersion vaccination. For this reason, in the current study we evaluated possible alternatives to a DNA-based i.m. injectable vaccine using the SVCV-G protein as the vaccine antigen. To this end, we tested two parallel approaches: the first based on the optimization of an alginate encapsulation method for oral delivery of DNA and protein antigens; the second based on the baculovirus recombinant expression of transmembrane SVCV-G protein in insect cells, administered as whole-cell subunit vaccine through the oral and injection route. In addition, in the case of the oral DNA vaccine, we also investigated the potential benefits of the mucosal adjuvants Escherichia coli lymphotoxin subunit B (LTB). Despite the use of various vaccine types, doses, regimes, and administration routes, no protection was observed, contrary to the full protection obtained with our reference i.m. DNA vaccine. The limited protection observed under the various conditions used in this study, the nature of the host, of the pathogen, the type of vaccine and encapsulation method, will therefore be discussed in details to provide an outlook for future vaccination strategies against SVCV.


Assuntos
Carpas , Doenças dos Peixes/prevenção & controle , Infecções por Rhabdoviridae/veterinária , Rhabdoviridae/imunologia , Vacinação/veterinária , Vacinas Virais/farmacologia , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/virologia , Células Sf9 , Spodoptera , Vacinas de DNA/administração & dosagem , Vacinas de DNA/classificação , Vacinas de DNA/farmacologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/classificação , Vacinas de Subunidades/farmacologia , Vacinas Virais/administração & dosagem , Vacinas Virais/classificação
7.
J Virol Methods ; 263: 14-19, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30336160

RESUMO

Spring viremia of carp, a fatal viral disease, is caused by the spring viremia of carp virus (SVCV) and can result in up to 70% mortalities in common carps and significant economic losses in several other cyprinid aquaculture. The present study aimed to investigate the possible control of SVCV replication in Epithelioma papulosum cyprini (EPC) cells using the RNA interference technology targeting the RNA-dependent RNA polymerase (L) gene of the SVCV that is essential for its replication. Three stealth small interfering RNA (siRNA) sequences were designed to target three different regions on the SVCV-L gene. The specific siRNAs designed were investigated individually or in combinations to inhibit the SVCV-L gene expression and the virus replication. Results showed that the most effective siRNA sequence was the siRNA-602 that specifically reduced the SVCV replication by two logs as indicated by the virus titration and quantitative real-time PCR. Results, also, showed that the minimum effective concentration of siRNA-602 was 20 nM when used to transfect the EPC cells before the virus inoculation. Results of this study clearly indicate that targeting the SVCV-L gene by RNAi can reduce the SVCV replication in vitro, that may lead to the control of SVCV in fish.


Assuntos
Interferência de RNA , RNA Replicase/genética , Infecções por Rhabdoviridae/virologia , Rhabdoviridae/fisiologia , Replicação Viral/genética , Animais , Carpas , Linhagem Celular Tumoral , Regulação Viral da Expressão Gênica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Infecções por Rhabdoviridae/prevenção & controle , Fatores de Tempo , Carga Viral
8.
Virology ; 525: 143-149, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30278384

RESUMO

The aquaculture industry is growing rapidly to meet the needs for global protein consumption. Viral diseases in aquaculture are quite challenging due to lack of treatment options as well as limited injection-delivery vaccines, which are costly. Thus, water-immersion antiviral treatments are highly desirable. This study focused on broad-spectrum, light-activated antivirals that target the viral membrane (envelope) of viruses to prevent viral-cell membrane fusion, ultimately blocking viral entry into cells. Of the tested small-molecules, JL122, a new broad-spectrum antiviral previously unexplored against aquatic viruses, blocked infection of three aquatic rhabdoviruses (IHNV, VHSV and SVCV) in cell culture and in two live fish challenge models. Importantly, JL122 inhibited transmission of IHNV from infected to uninfected rainbow trout. Further, the effective antiviral concentrations were not toxic to cells or susceptible fish. These results show promise for JL122 to become an immersion treatment option for outbreaks of aquatic enveloped viral infections.


Assuntos
Antivirais/uso terapêutico , Doenças dos Peixes/virologia , Vírus da Necrose Hematopoética Infecciosa , Novirhabdovirus , Oncorhynchus mykiss , Infecções por Rhabdoviridae/veterinária , Animais , Antivirais/classificação , Linhagem Celular Tumoral , Doenças dos Peixes/tratamento farmacológico , Estrutura Molecular , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/virologia , Relação Estrutura-Atividade
9.
Fish Shellfish Immunol ; 83: 84-95, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30195914

RESUMO

In the past decades, global freshwater fish production has been rapidly growing, while cyprinid takes the largest portion. Along with the rapid rise of novel forms of intensive aquaculture, increased global aquatic animal movement and various anthropogenic stress to aquatic ecosystems during the past century, freshwater fish farming industry encounter the emergence and breakout of many diseases, especially viral diseases. Because of the ability to safely and effectively prevent aquaculture diseases, vaccines have become the mainstream technology for prevention and control of aquatic diseases in the world. In this review, authors summarized six major cyprinid viral diseases, including koi herpesvirus disease (KHVD), spring viraemia of carp (SVC), grass carp hemorrhagic disease (GCHD), koi sleepy disease (KSD), carp pox disease (CPD) and herpesviral haematopoietic necrosis (HPHN). The present review described the characteristics of these diseases from epidemiology, pathology, etiology and diagnostics. Furthermore, the development of specific vaccines respective to these diseases is stated according to preparation methods and immunization approaches. It is hoped that the review could contribute to aquaculture in prevention and controlling of cyprinid viral diseases, and serve the healthy and sustainable development of aquaculture industry.


Assuntos
Cyprinidae/virologia , Doenças dos Peixes/prevenção & controle , Infecções por Herpesviridae/veterinária , Infecções por Rhabdoviridae/veterinária , Vacinas Virais/imunologia , Viroses/veterinária , Animais , Aquicultura , Cyprinidae/imunologia , Doenças dos Peixes/virologia , Herpesviridae/imunologia , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/prevenção & controle , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Viroses/prevenção & controle
10.
J Gen Virol ; 99(12): 1590-1599, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29745870

RESUMO

The lyssaviruses are an important group of viruses that cause a fatal encephalitis termed rabies. The prototypic lyssavirus, rabies virus, is predicted to cause more than 60 000 human fatalities annually. The burden of disease for the other lyssaviruses is undefined. The original reports for the recently described highly divergent Lleida bat lyssavirus were based on the detection of virus sequence alone. The successful isolation of live Lleida bat lyssavirus from the carcass of the original bat and in vitro characterization of this novel lyssavirus are described here. In addition, the ability of a human rabies vaccine to confer protective immunity following challenge with this divergent lyssavirus was assessed. Two different doses of Lleida bat lyssavirus were used to challenge vaccinated or naïve mice: a high dose of 100 focus-forming units (f.f.u.) 30 µl-1 and a 100-fold dilution of this dose, 1 f.f.u. 30 µl-1. Although all naïve control mice succumbed to the 100 f.f.u. 30 µl-1 challenge, 42 % (n=5/12) of those infected intracerebrally with 1 f.f.u. 30 µl-1 survived the challenge. In the high-challenge-dose group, 42 % of the vaccinated mice survived the challenge (n=5/12), whilst at the lower challenge dose, 33 % (n=4/12) survived to the end of the experiment. Interestingly, a high proportion of mice demonstrated a measurable virus-neutralizing antibody response, demonstrating that neutralizing antibody titres do not necessarily correlate with the outcome of infection via the intracerebral route. Assessing the ability of existing rabies vaccines to protect against novel divergent lyssaviruses is important for the development of future public health strategies.


Assuntos
Antígenos Virais/imunologia , Quirópteros/virologia , Proteção Cruzada , Lyssavirus/classificação , Lyssavirus/isolamento & purificação , Vacinas Antirrábicas/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Lyssavirus/imunologia , Camundongos , Análise de Sobrevida
11.
Fish Shellfish Immunol ; 79: 256-264, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29777766

RESUMO

To elicit the immune protective of vaccine against the highly contagious and pathogenic disease caused by spring viremia of carp virus (SVCV), a novel functionalized single-walled carbon nanotubes (SWCNTs) were applied as a delivery vehicle for DNA vaccine. In this study, we report a SWCNTs-DNA vaccine encoding matrix protein of SVCV which, when injected in the muscle at a dose of 10 µg SWCNTs-pcDNA-M vaccine, confers up to 51.3% protection against intraperitoneal challenge with SVCV. In addition, SWCNTs as a promising vehicle can enhance about 17.5% of the immune protective effect in SWCNTs-pcDNA-M vaccinated common carp compared with fish injected with naked pcDNA-M DNA vaccine. In addition, serum antibody production, none specific immunity parameters (complement activity, superoxide dismutase activity (SOD), acid phosphatase activity (ACP) and alkaline phosphatase activity (AKP)) and immune-related genes were used to verify the enhancement immune response induced in SWCNTs-pcDNA-M vaccinated fish, herein all these mentioned immune activities were significantly enhanced after immunization. Thereby, it is revealed that the M gene of SVCV could be used as an antigen for DNA vaccine constructs, and SWCNTs could be a candidate DNA vaccine carrier to enhance the immunological response against fish disease.


Assuntos
Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Nanotubos de Carbono/análise , Rhabdoviridae/imunologia , Vacinação/veterinária , Vacinas Virais/imunologia , Animais , Injeções Intramusculares/veterinária , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/veterinária , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Proteínas da Matriz Viral/imunologia , Vacinas Virais/administração & dosagem
12.
J S Afr Vet Assoc ; 89(0): e1-e13, 2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29781673

RESUMO

Both domestic and wild carnivore species are commonly diagnosed with rabies virus (RABV) infection in South Africa. Although the majority of confirmed rabies cases in wild carnivore species are reported from the yellow mongoose (Cynictis penicillata), the rest are from other wild carnivores including the highly endangered wild dog (Lycaon pictus). Lyssavirus infection was confirmed in two wild dogs and a spotted hyaena (Crocuta crocuta) in the Madikwe Game Reserve, North West province in South Africa, in 2014 and 2015, using a direct fluorescent antibody test and immunohistochemistry. There had been no new wild dog introductions to the Madikwe Game Reserve for many years and the wild dogs were last vaccinated against rabies approximately 11 years prior to the incident. The first euthanised wild dog was the last surviving of a break-away pack of 6, and the second was the last of a larger pack of 18, the rest of which died with no carcasses being found or carcasses too decomposed for sampling. Subsequent antigenic typing of the lyssaviruses indicated that they were canid RABVs. The RABVs originating from 22 wild carnivore species, 7 dogs, and a caprine, mostly from the North West province, were genetically characterised by targeting a partial region of the nucleoprotein gene. The nucleotide sequence analyses of these viruses and two previously characterised RABVs confirmed that the outbreak viruses were also canid rabies, phylogenetically clustering with virus isolates originating from black-backed jackals recovered between 2012 and 2015 from the North West province, and domestic dogs from neighbouring communal areas. The source(s) of the mortalities and possible reservoir host(s) for the virus could only be speculated upon from data on specific predator numbers, movements and behaviour, kills, park management and the changing environmental ecology, which were monitored closely in Madikwe over several years. The most likely rabies sources were from boundary fence contacts between wild carnivores within the park, with domestic dogs or cats and/or naturally occurring wild carnivores outside the park. The associated risk of zoonotic infection and threat to important and endangered predators may be mitigated through regional rabies control primarily in domestic dogs and cats, as well as by preventative vaccination of at-risk park employees and their pets. The importance of ongoing prophylactic rabies protection by regular vaccination of highly endangered wildlife carnivores and the submission of carcasses for rabies diagnosis of any wild or domestic animals behaving uncharacteristically or found dead is emphasised.


Assuntos
Animais Selvagens/virologia , Canidae/virologia , Hyaenidae/virologia , Infecções por Rhabdoviridae/veterinária , Animais , Animais de Zoológico , Encéfalo/virologia , Surtos de Doenças/prevenção & controle , Cães , Espécies em Perigo de Extinção , Humanos , Imunoquímica , Lyssavirus/isolamento & purificação , Masculino , Raiva , Vacinas Antirrábicas , Infecções por Rhabdoviridae/diagnóstico , Infecções por Rhabdoviridae/epidemiologia , Infecções por Rhabdoviridae/prevenção & controle , África do Sul/epidemiologia , Zoonoses/prevenção & controle
13.
Fish Shellfish Immunol ; 77: 474-480, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29604344

RESUMO

In order to develop live vaccine against Siniperca chuatsi rhabdovirus (SCRV) disease, an avirulent virus strain, designed as Micropterus salmoides rhabdovirus Sanshui (MSRV-SS), was selected from six fish rhabdovirus isolates (SCRV-QY、SCRV-SS、SCRV-GM、CMRV-FS、OMBRV-JM、MSRV-SS) by fish challenge assay. When Chinese perch (Siniperca chuatsi) were intraperitoneally injected live virus strain MSRV-SS, they were completely protected from virulent SCRV-GM challenge with a relative percent survival (RPS) of 100% on 18th day post vaccination. Then, the wild type MSRV-SS was purified by plaque clone assays, and the biological characteristics of the clonal strain designed as MSRV-SS-7 were investigated. The MSRV-SS-7 was avirulent to Chinese perch and its growth characteristic was similar to the MSRV-SS. The immune protection effects of clonal MSRV-SS-7 against virulent SCRV-GM were evaluated by intraperitoneal injection (IP) vaccination and immersion (IM) vaccination, their RPSs were all 100%. Altogether, these results indicate that MSRV-SS-7 is a potential live vaccine candidate against SCRV disease.


Assuntos
Doenças dos Peixes/prevenção & controle , Perciformes , Infecções por Rhabdoviridae/veterinária , Rhabdoviridae/imunologia , Vacinação/veterinária , Vacinas Virais/imunologia , Animais , Bass/virologia , Doenças dos Peixes/virologia , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/virologia
14.
Viruses ; 10(3)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29543715

RESUMO

Lyssaviruses constitute a diverse range of viruses with the ability to cause fatal encephalitis known as rabies. Existing human rabies vaccines and post exposure prophylaxes (PEP) are based on inactivated preparations of, and neutralising antibody preparations directed against, classical rabies viruses, respectively. Whilst these prophylaxes are highly efficient at neutralising and preventing a productive infection with rabies virus, their ability to neutralise other lyssaviruses is thought to be limited. The remaining 15 virus species within the lyssavirus genus have been divided into at least three phylogroups that generally predict vaccine protection. Existing rabies vaccines afford protection against phylogroup I viruses but offer little to no protection against phylogroup II and III viruses. As such, work involving sharps with phylogroup II and III must be considered of high risk as no PEP is thought to have any effect on the prevention of a productive infection with these lyssaviruses. Whilst rabies virus itself has been characterised in a number of different animal models, data on the remaining lyssaviruses are scarce. As the lyssavirus glycoprotein is considered to be the sole target of neutralising antibodies we generated a vaccine strain of rabies using reverse genetics expressing highly divergent glycoproteins of West Caucasian Bat lyssavirus and Ikoma lyssavirus. Using these recombinants, we propose that recombinant vaccine strain derived lyssaviruses containing heterologous glycoproteins may be a suitable surrogate for wildtype viruses when assessing vaccine protection for the lyssaviruses.


Assuntos
Lyssavirus/genética , Lyssavirus/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linhagem Celular , Quirópteros/virologia , Camundongos , Raiva/imunologia , Raiva/prevenção & controle , Vacinas Antirrábicas/imunologia , Vírus da Raiva/genética , Vírus da Raiva/imunologia
15.
J Gen Virol ; 99(2): 169-180, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29300155

RESUMO

Lyssavirus infection has a near 100 % case fatality rate following the onset of clinical disease, and current rabies vaccines confer protection against all reported phylogroup I lyssaviruses. However, there is little or no protection against more divergent lyssaviruses and so investigation into epitopes within the glycoprotein (G) that dictate a neutralizing response against divergent lyssaviruses is warranted. Importantly, the facilities required to work with these pathogens, including wild-type and mutated forms of different lyssaviruses, are scarcely available and, as such, this type of study is inherently difficult to perform. The relevance of proposed immunogenic antigenic sites within the lyssavirus glycoprotein was assessed by swapping sites between phylogroup-I and -II glycoproteins. Demonstrable intra- but limited inter-phylogroup cross-neutralization was observed. Pseudotype viruses (PTVs) presenting a phylogroup-I glycoprotein containing phylogroup-II antigenic sites (I, II III or IV) were neutralized by antibodies raised against phylogroup-II PTV with the site II (IIb, aa 34-42 and IIa, aa 198-200)-swapped PTVs being efficiently neutralized, whilst site IV-swapped PTV was poorly neutralized. Specific antibodies raised against PTV-containing antigenic site swaps between phylogroup-I and -II glycoproteins neutralized phylogroup-I PTVs efficiently, indicating an immunodominance of antigenic site II. Live lyssaviruses containing antigenic site-swapped glycoproteins were generated and indicated that specific residues within the lyssavirus glycoprotein dictate functionality and enable differential neutralizing antibody responses to lyssaviruses.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Glicoproteínas/imunologia , Lyssavirus/imunologia , Vacinas Antirrábicas/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Animais , Anticorpos Neutralizantes/imunologia , Antígenos Virais/imunologia , Modelos Animais de Doenças , Cães , Epitopos/genética , Epitopos/imunologia , Feminino , Glicoproteínas/genética , Humanos , Lyssavirus/genética , Camundongos , Mutação , Raiva/imunologia , Raiva/prevenção & controle , Raiva/virologia , Vírus da Raiva/genética , Vírus da Raiva/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/virologia
16.
J Fish Dis ; 41(1): 67-78, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28799647

RESUMO

Infectious haematopoietic necrosis virus (IHNV) and spring viraemia of carp virus (SVCV) are both rhabdoviruses of fish, listed as notifiable disease agents by the World Organization for Animal Health. Recombinant rhabdoviruses with heterologous gene substitutions have been engineered to study genetic determinants and assess the potential of these recombinant viruses for vaccine development. A recombinant IHNV (rIHNV), containing the full-length genome of a European IHNV strain, was modified by deleting the glycoprotein (G) gene and replacing it with a European SVCV G-gene to make the rIHNV-Gsvcv. The chimeric rIHNV-Gsvcv level of virulence in rainbow trout, common carp and koi was assessed, and its ability to induce a protective immune response in surviving koi against wild-type SVCV infection was tested. The rIHNV-Gsvcv infection of trout led to high mortality, ranging from 78% to 92.5%, after immersion. In contrast, no deaths occurred in juvenile common carp after infection with rIHNV-Gsvcv by either immersion or intraperitoneal (IP) injection. Similarly, koi infected with rIHNV-Gsvcv via IP injection had little to no mortality (≤9%). Koi that survived initial infection with a high dose of recombinant virus rIHNV-Gsvcv were protected against a virulent SVCV challenge resulting in a high relative per cent survival of 82.5%.


Assuntos
Carpas/virologia , Vírus da Necrose Hematopoética Infecciosa/patogenicidade , Oncorhynchus mykiss/virologia , Infecções por Rhabdoviridae/veterinária , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/virologia , Glicoproteínas/genética , Vírus da Necrose Hematopoética Infecciosa/genética , Vírus da Necrose Hematopoética Infecciosa/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Vesiculovirus/genética , Vacinas Virais/biossíntese , Vacinas Virais/genética , Vacinas Virais/imunologia , Virulência
17.
Acta Vet Scand ; 59(1): 64, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-28969696

RESUMO

BACKGROUND: Rabies is preventable by pre- and/or post-exposure prophylaxis consisting of series of rabies vaccinations and in some cases the use of immunoglobulins. The success of vaccination can be estimated either by measuring virus neutralising antibodies or by challenge experiment. Vaccines based on rabies virus offer cross-protection against other lyssaviruses closely related to rabies virus. The aim was to assess the success of rabies vaccination measured by the antibody response in dogs (n = 10,071) and cats (n = 722), as well as to investigate the factors influencing the response to vaccination when animals failed to reach a rabies antibody titre of ≥ 0.5 IU/ml. Another aim was to assess the level of protection afforded by a commercial veterinary rabies vaccine against intracerebral challenge in mice with European bat lyssavirus type 2 (EBLV-2) and classical rabies virus (RABV), and to compare this with the protection offered by a vaccine for humans. RESULTS: A significantly higher proportion of dogs (10.7%, 95% confidence interval CI 10.1-11.3) than cats (3.5%; 95% CI 2.3-5.0) had a vaccination antibody titre of < 0.5 IU/ml. In dogs, vaccination with certain vaccines, vaccination over 6 months prior the time of antibody determination and vaccination of dogs with a size of > 60 cm or larger resulted in a higher risk of failing to reach an antibody level of at least 0.5 IU/ml. When challenged with EBLV-2 and RABV, 80 and 100% of mice vaccinated with the veterinary rabies vaccine survived, respectively. When mice were vaccinated with the human rabies vaccine and challenged with EBLV-2, 75-80% survived, depending on the booster. All vaccinated mice developed sufficient to high titres of virus-neutralising antibodies (VNA) against RABV 21-22 days post-vaccination, ranging from 0.5 to 128 IU/ml. However, there was significant difference between antibody titres after vaccinating once in comparison to vaccinating twice (P < 0.05). CONCLUSIONS: There was a significant difference between dogs and cats in their ability to reach a post vaccination antibody titre of ≥ 0.5 IU/ml. Mice vaccinated with RABV-based rabies vaccines were partly cross-protected against EBLV-2, but there was no clear correlation between VNA titres and cross-protection against EBLV-2. Measurement of the RABV VNA titre can only be seen as a partial tool to estimate the cross-protection against other lyssaviruses. Booster vaccination is recommended for dogs and cats if exposed to infected bats.


Assuntos
Lyssavirus/imunologia , Vacinas Antirrábicas/uso terapêutico , Infecções por Rhabdoviridae/veterinária , Animais , Gatos , Cães , Feminino , Finlândia , Masculino , Camundongos , Vacinas Antirrábicas/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle
18.
Natl Med J India ; 30(1): 21-25, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28731002

RESUMO

Chandipura virus (CHPV) has been contributing to the rising number of premature deaths due to acute encephalitis syndrome for over a decade in India. CHPV belongs to the family Rhabdoviridae. Neuropathogenesis of CHPV has been well established but the exact route of entry into the central nervous system (CNS) and the triggering factor for neuronal death are still unknown. Rabies virus and vesicular stomatitis virus, which are related closely to CHPV, enter the CNS retrogradely from peripheral or olfactory neurons. Disruption of the blood-brain barrier has also been connoted in the entry of CHPV into the CNS. CHPV upon entering the neurons triggers cellular stress factors and release of reactive oxygen species (ROS). The stress granules produced in response to cellular stress have been implicated in viral replication and ROS generation, which stimulates neuronal death. Both these phenomena cohesively explain the neuropathogenesis and neurodegeneration following CHPV infection.


Assuntos
Encefalopatia Aguda Febril/epidemiologia , Doenças Endêmicas/estatística & dados numéricos , Infecções por Rhabdoviridae/epidemiologia , Vesiculovirus/patogenicidade , Zoonoses/epidemiologia , Encefalopatia Aguda Febril/prevenção & controle , Encefalopatia Aguda Febril/virologia , Animais , Doenças Endêmicas/prevenção & controle , Humanos , Índia/epidemiologia , Mosquitos Vetores/virologia , Psychodidae/virologia , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/transmissão , Infecções por Rhabdoviridae/virologia , Vesiculovirus/isolamento & purificação , Vesiculovirus/fisiologia , Zoonoses/prevenção & controle , Zoonoses/transmissão , Zoonoses/virologia
19.
Sci Rep ; 7(1): 5700, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28720888

RESUMO

Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are important pathogens of salmon and trout. An active bivalent DNA vaccine was constructed with the glycoprotein gene of Chinese IHNV isolate Sn1203 and VP2-VP3 gene of Chinese IPNV isolate ChRtm213. Rainbow trout (5 g) were vaccinated by intramuscular injection with 1.0 µg of the bivalent DNA vaccine and then challenged with an intraperitoneal injection of IHNV, IPNV, or both, at 30 and 60 days post-vaccination (d.p.v.). High protection rates against IHNV were observed, with 6% and 10% cumulative mortality, respectively, compared with 90-94% in the mock-vaccinated groups. IPNV loads (531-fold and 135-fold, respectively) were significantly reduced in the anterior kidneys of the vaccinated trout. Significant protection against co-infection with IHNV and IPNV was observed, with cumulative mortality rates of 6.67% and 3.33%, respectively, compared with 50.0% and 43.3%, respectively, in the mock-vaccinated groups. No detectable infective IHNV or IPNV was recovered from vaccinated trout co-infected with IHNV and IPNV. The bivalent DNA vaccine increased the expression of Mx-1 and IFN-γ at 4, 7, and 15 d.p.v, and IgM at 21 d.p.v., and induced high titres (≥160) of IHNV and IPNV neutralizing antibodies at 30 and 60 d.p.v.


Assuntos
Infecções por Birnaviridae/veterinária , Doenças dos Peixes/imunologia , Vírus da Necrose Hematopoética Infecciosa/imunologia , Vírus da Necrose Pancreática Infecciosa/imunologia , Oncorhynchus mykiss , Infecções por Rhabdoviridae/veterinária , Vacinas de DNA/imunologia , Animais , Anticorpos Antivirais , Infecções por Birnaviridae/imunologia , Infecções por Birnaviridae/prevenção & controle , Coinfecção/imunologia , Coinfecção/veterinária , Coinfecção/virologia , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/virologia , Rim Cefálico/virologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/prevenção & controle , Vacinas Virais/imunologia
20.
Vaccine ; 35(18): 2420-2426, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28343776

RESUMO

Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In this study, a DNA vaccine, designated pIHNch-G, was constructed with the glycoprotein (G) gene of a Chinese IHNV isolate SD-12 (also called Sn1203) of genotype J. The minimal dose of vaccine required, the expression of the Mx-1 gene in the muscle (vaccine delivery site) and anterior kidney, and the titers of the neutralizing antibodies produced were used to evaluate the vaccine efficacy. To assess the potential utility of the vaccine in controlling IHNV throughout China, the cross protective efficacy of the vaccine was determined by challenging fish with a broad range of IHNV strains from different geographic locations in China. A single 100ng dose of the vaccine conferred almost full protection to rainbow trout fry (3g) against waterborne or intraperitoneal injection challenge with IHNV strain SD-12 as early as 4days post-vaccination (d.p.v.), and significant protection was still observed at 180d.p.v. Intragenogroup challenges showed that the DNA vaccine provided similar protection to the fish against all the Chinese IHNV isolates tested, suggesting that the vaccine can be widely used in China. Mx-1 gene expression was significantly upregulated in the muscle tissue (vaccine delivery site) and anterior kidney in the vaccinated rainbow trout at both 4 and 7d.p.v. Similar levels of neutralizing antibodies were determined with each of the Chinese IHNV strains at 60 and 180d.p.v. This DNA vaccine should play an important role in the control of IHN in China.


Assuntos
Doenças dos Peixes/prevenção & controle , Vírus da Necrose Hematopoética Infecciosa/imunologia , Infecções por Rhabdoviridae/veterinária , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Estruturas Animais/virologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , China , Proteção Cruzada , Doenças dos Peixes/virologia , Perfilação da Expressão Gênica , Genótipo , Vírus da Necrose Hematopoética Infecciosa/genética , Infecções por Rhabdoviridae/prevenção & controle , Salmonidae , Resultado do Tratamento , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
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