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1.
Sci Rep ; 14(1): 10169, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702375

RESUMO

Bovine viral diarrhea virus (BVDV) is considered to be the most common agent of severe diarrhea in cattle worldwide, causing fever, diarrhea, ulcers, and abortion. Bovine herpesvirus 1 (BoHV-1) is also a major bovine respiratory disease agent that spreads worldwide and causes extensive damage to the livestock industry. Recombinase polymerase amplification (RPA) is a novel nucleic acid amplification method with the advantages of high efficiency, rapidity and sensitivity, which has been widely used in the diagnosis of infectious diseases. A dual RPA assay was developed for the simultaneous detection of BVDV and BoHV-1. The assay was completed at a constant temperature of 37 °C for 30 min. It was highly sensitive and had no cross-reactivity with other common bovine viruses. The detection rate of BVDV RPA in clinical samples (36.67%) was higher than that of PCR (33.33%), the detection rate of BoHV-1 RPA and PCR were equal. Therefore, the established dual RPA assay for BVDV and BoHV-1 could be a potential candidate for use as an immediate diagnostic.


Assuntos
Vírus da Diarreia Viral Bovina , Herpesvirus Bovino 1 , Técnicas de Amplificação de Ácido Nucleico , Recombinases , Animais , Bovinos , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Recombinases/metabolismo , Vírus da Diarreia Viral Bovina/genética , Vírus da Diarreia Viral Bovina/isolamento & purificação , Sensibilidade e Especificidade , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/diagnóstico , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/diagnóstico , DNA Viral/genética
2.
Front Immunol ; 15: 1367253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646533

RESUMO

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.


Assuntos
Herpesvirus Bovino 1 , Mycoplasma bovis , Vacinas Atenuadas , Vacinas Combinadas , Animais , Bovinos , Herpesvirus Bovino 1/imunologia , Vacinas Combinadas/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Mycoplasma bovis/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/efeitos adversos , Citocinas/metabolismo , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Infecções por Mycoplasma/prevenção & controle , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/imunologia , Vacinas Marcadoras/imunologia , Vacinas Marcadoras/administração & dosagem , Vacinação/veterinária , Eficácia de Vacinas , Imunidade Humoral , Complexo Respiratório Bovino/prevenção & controle , Complexo Respiratório Bovino/imunologia , Complexo Respiratório Bovino/virologia
3.
Am J Vet Res ; 85(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38457927

RESUMO

OBJECTIVE: Compare immune responses induced by 2 commercial intranasal (IN) modified-live viral (MLV) vaccines given individually or coadministered and evaluate prevention of infection and lung pathology following bovine herpesvirus-1 (BHV-1) challenge. ANIMALS: 36 male Holstein calves (ages, 5 to 12 days). METHODS: In a randomized complete block design, each calf received an IN injection of either vaccine diluent (Placebo), an MLV vaccine containing bovine herpesvirus-1 (BHV-1; N3), bovine coronavirus vaccine (BC), or both N3 and BC (BC + N3) with a booster 4 weeks later. Nasal secretions and blood were collected weekly. Three weeks after the booster, the calves were challenged with BHV-1, sampled for virus shedding, and euthanized 10 days later to quantify lung pathology. The study period was September 7, 2020, to April 6, 2021. RESULTS: Calves were seropositive for BHV-1 and BC before vaccination. No significant difference in BC-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the BC versus BC + N3 group or BHV-1-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the N3 versus BC + N3 group. Cytokine responses to BHV-1 and BC did not differ among groups. BHV-1 shedding after challenge was significantly reduced in N3 groups versus Placebo and BC. There was a significant reduction in lung pathology in the N3 + BC group versus Placebo. CLINICAL RELEVANCE: This study provides evidence an MLV vaccine containing BHV-1 and an MLV BC vaccine can be coadministered to neonatal calves without significantly altering immune responses to the 2 viruses or compromising the prevention of BHV-1 respiratory disease. Calves receiving the BC + N3 vaccine had a significant reduction in lung pathology after BHV-1 aerosol challenge.


Assuntos
Administração Intranasal , Animais Recém-Nascidos , Doenças dos Bovinos , Infecções por Coronavirus , Coronavirus Bovino , Infecções por Herpesviridae , Herpesvirus Bovino 1 , Vacinas Atenuadas , Vacinas Virais , Animais , Bovinos , Herpesvirus Bovino 1/imunologia , Administração Intranasal/veterinária , Masculino , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Coronavirus Bovino/imunologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Doenças dos Bovinos/imunologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Rinotraqueíte Infecciosa Bovina/imunologia , Eliminação de Partículas Virais , Anticorpos Antivirais/sangue , Distribuição Aleatória
4.
Vet Immunol Immunopathol ; 269: 110726, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341929

RESUMO

Probiotics are live microorganisms that, confer health benefits to the host when supplemented in adequate amounts. They can promote immunomodulation by inducing phagocyte activity, leukocyte proliferation, antibody production, and cytokine expression. Lactic acid bacteria (BAL) are important probiotic specimens with properties that can improves ruminant nutrition, productivity and immunity. The aim of the present study was to evaluate the immunomodulatory effect of the supplementation with Lacticaseibacillus casei CB054 in calve vaccinated against bovine infectious rhinotracheitis (IBR). Calve were vaccinated with a commercial IBR vaccine, on day 0 and received a booster dose on day 21. L. casei CB054 was orally administered (4 ×109 UFC) for 35 days, while a non-supplemented control group received Phosphate Buffer Saline (PBS). Stimulation of bovine splenocytes with L. casei CB054 markedly enhanced mRNA transcription levels of cytokines IL2, IL4, IL10 and IL17 genes. Calves supplemented with L. casei CB054 showed significantly higher (p < 0.05) specific anti-BoHV-1 IgG levels, higher serum neutralization, as well as higher mRNA transcription for IL2, IL4, IL10 and IL17 genes in Peripheral Blood Mononuclear Cells (PBMCs) comparing with control calves. Supplemented calve had an average weight gain of ∼14 kg more than non-supplemented during the experimental period. These results suggest that L. casei CB054 supplementation increase immunogenicity of a commercial IBR vaccine in cattle and improve weight gain.


Assuntos
Doenças dos Bovinos , Herpesvirus Bovino 1 , Rinotraqueíte Infecciosa Bovina , Lacticaseibacillus casei , Vacinas , Animais , Bovinos , Interleucina-10 , Interleucina-2 , Interleucina-4 , Leucócitos Mononucleares , Citocinas , Suplementos Nutricionais , Imunomodulação , Aumento de Peso , RNA Mensageiro , Doenças dos Bovinos/prevenção & controle
5.
Viruses ; 16(2)2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400086

RESUMO

The CRISPR/Cas9 system is widely used to manipulate viral genomes. Although Alphaherpesvirinae genomes are large and complicated to edit, in recent years several Pseudorabies virus (PRV) mutants have been successfully generated using the CRISPR/Cas9 system. However, the application of CRISPR/Cas9 editing on another member of alpha herpesviruses, bovine herpesvirus-1 (BHV-1), is rarely reported. This paper reports a rapid and straightforward approach to manipulating herpesviruses genome using CRISPR/Cas9. The recombinant plasmids contained the left and right arm of the thymidine kinase (TK) gene of PRV or of the glycoprotein I (gI) and glycoprotein E (gE) of BHV-1. Upon the cleavage of the TK or gIgE gene by Cas9 protein, this was replaced by the enhanced green fluorescence protein (eGFP) by homologous recombination. With this approach, we generated recombinant TK-/eGFP+ PRV and gIgE-/eGFP+ BHV-1 mutants and then proceeded to characterize their biological activities in vitro and in vivo. In conclusion, we showed that alpha herpesvirus, including PRV and BHV-1, can be rapidly edited using the CRISPR/Cas9 approach paving the way to the development of animal herpesvirus vaccines.


Assuntos
Herpesvirus Bovino 1 , Herpesvirus Suídeo 1 , Pseudorraiva , Animais , Edição de Genes , Sistemas CRISPR-Cas , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/metabolismo , Pseudorraiva/prevenção & controle , Glicoproteínas/genética
6.
Vet Microbiol ; 291: 110031, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38412580

RESUMO

Bovine herpesvirus 1 (BoHV-1) is a highly contagious pathogen which causes infectious bovine rhinotracheitis in cattle worldwide. Although it has the ability to evade the host's antiviral innate immune response and establish persistent latent infections, the mechanisms are not fully understood, especially the function of the tegument protein to escape innate immunity and participate in viral replication. In this study, we showed that overexpression of tegument protein UL3 facilitates BoHV-1 replication and suppresses the expression of type-I interferon (IFN-I) and IFN-stimulated genes. Then, STING was identified as the target by which UL3 inhibits the IFN-I signaling pathway, and STING was degraded through the UL3-induced autophagy pathway. Furthermore, overexpression of UL3 promotes the expression of the autophagy-related protein ATG101, thereby inducing autophagy. Further study showed that UL3 enhances the interaction between ATG101 and STING, and then the degradation of STING was reversed following ATG101 silencing in UL3-overexpressing cells during BoHV-1 infection. Our research results demonstrate a novel function of UL3 in regulating host's antiviral response and provide a potential mechanism for BoHV-1 immune evasion.


Assuntos
Infecções por Herpesviridae , Herpesvirus Bovino 1 , Proteínas Virais , Animais , Bovinos , Antivirais , Autofagia , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/metabolismo , Imunidade Inata/genética , Replicação Viral/genética , Interferon Tipo I/metabolismo , Proteínas de Membrana/metabolismo , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/veterinária , Proteínas Virais/metabolismo
7.
BMC Genomics ; 25(1): 158, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331736

RESUMO

BACKGROUND: Studies have confirmed that Infectious bovine rhinotracheitis virus (IBRV) infection induces mitochondrial damage. MicroRNAs (miRNAs) are a class of noncoding RNA molecules, which are involved in various biological processes and pathological changes associated with mitochondrial damage. It is currently unclear whether miRNAs participate in IBRV-induced mitochondrial damage in Madin-Darby bovine kidney (MDBK) cells. RESULTS: In the present study, we used high-throughput sequencing technology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for mitochondria-related miRNAs and messenger RNAs (mRNAs). In total, 279 differentially expressed miRNAs and 832 differentially expressed mRNAs were identified in 6 hours (IBRV1) versus 24 hours (IBRV2) after IBRV infection in MDBK cells. GO and KEGG enrichment analysis revealed that 42 differentially expressed mRNAs and 348 target genes of differentially expressed miRNAs were correlated with mitochondrial damage, and the miRNA-mitochondria-related target genes regulatory network was constructed to elucidate their potential regulatory relationships. Among the 10 differentially expressed miRNAs, 8 showed expression patterns consistent with the high-throughput sequencing results. Functional validation results showed that overexpression of miR-10a and miR-182 aggravated mitochondrial damage, while inhibition of miR-10a and miR-182 alleviated mitochondrial damage. CONCLUSIONS: This study not only revealed the expression changes of miRNAs and mRNAs in IBRV-infected MDBK cells, but also revealed possible biological regulatory relationship between them. MiR-10a and miR-182 may have the potential to be developed as biomarkers for the diagnosis and treatment of IBRV. Together, Together, these data and analyses provide additional insights into the roles of miRNA and mRNA in IBRV-induced mitochondria damage.


Assuntos
Herpesvirus Bovino 1 , MicroRNAs , Animais , Bovinos , MicroRNAs/genética , MicroRNAs/metabolismo , Herpesvirus Bovino 1/genética , Células Epiteliais/metabolismo , Rim/metabolismo , Redes Reguladoras de Genes , RNA Mensageiro/genética , Perfilação da Expressão Gênica
8.
Virology ; 593: 110012, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38367473

RESUMO

Using marker vaccines to control bovine alphaherpesvirus-1 (BoHV-1) is a novel strategy for differentiation between infected and vaccinated animals (DIVA). In this study, multiplex real-time PCR targeting gD and gE genes was applied for BoHV-1 screening on 60 clinical samples from cattle with a history of vaccination, in some cases by US2-deleted marker vaccines, that were suffering from severe respiratory symptoms. Conventional PCR targeting the gC and US2 flanking region was done for molecular characterization and identification of the US2-deleted vaccine strain. Six samples were positive for BoHV-1 by both RT-PCR and conventional PCR. Surprisingly, a conventional PCR DIVA trial based on the US2 gene revealed that only one sample that exhibited the US2 gene was a wild virus, while others that did not exhibit the US2 gene were vaccine viruses. Phylogenetic characterization classifies the samples as BoHV-1.1. This finding reveals the circulation of vaccine virus in field-diseased animals, which threatens the eradication program.


Assuntos
Doenças dos Bovinos , Infecções por Herpesviridae , Herpesvirus Bovino 1 , Animais , Bovinos , Herpesvirus Bovino 1/genética , Vacinas Marcadoras/genética , Egito/epidemiologia , Filogenia , Reação em Cadeia da Polimerase em Tempo Real
9.
Am J Vet Res ; 85(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38422620

RESUMO

OBJECTIVE: To determine the efficacy of primary or booster intranasal vaccination of beef steers on clinical protection and pathogen detection following simultaneous challenge with bovine respiratory syncytial virus and bovine herpes virus 1. METHODS: 30 beef steers were randomly allocated to 3 different treatment groups starting at 2 months of age. Group A (n = 10) was administered a single dose of a parenteral modified-live vaccine and was moved to a separate pasture. Groups B (n = 10) and C (10) remained unvaccinated. At 6 months of age, all steers were weaned and transported. Subsequently, groups A and B received a single dose of an intranasal modified-live vaccine vaccine while group C remained unvaccinated. Group C was housed separately until challenge. Two days following vaccination, all steers were challenged with bovine respiratory syncytial virus and bovine herpes virus 1 and housed in a single pen. Clinical and antibody response outcomes and the presence of nasal pathogens were evaluated. RESULTS: The odds of clinical disease were lower in group A compared with group C on day 7 postchallenge; however, antibody responses and pathogen detection were not significantly different between groups before and following viral challenge. All calves remained negative for Histophilus somni and Mycoplasma bovis; however, significantly greater loads of Mannheimia haemolytica and Pasteurella multocida were detected on day 7 postchallenge compared with day -2 prechallenge. CLINICAL RELEVANCE: Intranasal booster vaccination of beef steers at 6 months of age reduced clinical disease early after viral challenge. Weaning, transport, and viral infection promoted increased detection rates of M haemolytica and P multocida regardless of vaccination status.


Assuntos
Administração Intranasal , Coinfecção , Herpesvirus Bovino 1 , Imunização Secundária , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Bovino , Animais , Bovinos , Herpesvirus Bovino 1/imunologia , Masculino , Administração Intranasal/veterinária , Vírus Sincicial Respiratório Bovino/imunologia , Imunização Secundária/veterinária , Coinfecção/veterinária , Coinfecção/prevenção & controle , Coinfecção/microbiologia , Infecções por Vírus Respiratório Sincicial/veterinária , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Rinotraqueíte Infecciosa Bovina/imunologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/virologia , Doenças dos Bovinos/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Derrame de Bactérias , Anticorpos Antivirais/sangue , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/prevenção & controle , Distribuição Aleatória , Vacinação/veterinária
10.
Sci Rep ; 14(1): 867, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195809

RESUMO

Surveillance of endemic pathogens is essential for disease control, providing an evidence base for policy and advice. Bovine Herpes Virus Type 1 (BoHV-1), the causative agent of Infectious Bovine Rhinotracheitis (IBR), has been found to have high seroprevalence within the Irish cattle population. The aim of the present study was to establish seroprevalence levels for culled cattle in Ireland aged < 30 months and to establish whether BVD exposure and other factors was associated with BoHV-1 exposure. We employed random effects logit models coupled with repeated bootstrap sampling to provide robust estimates. The final dataset contained results for 5273 animals tested over two study years, 2018 and 2020. The animal-level seroprevalence of BoHV-1 was 21.43% (1130/5273; 95%CI: 20.32-22.53%). Univariable analysis suggested that BoHV-1 seropositivity risk was associated with BVDV serodiagnosis status, age, sex, year sampled, herd type, herd-size, and metrics of movement into the herd. Final random-effects multivariable models suggested increased risk associated with increasing herd size of the last herd, movements made by animals during the previous year, and the year the animal was sampled. Despite BVDV status and sex being retained in the final model, repeated bootstrap sampling of the regression model to estimate biased-corrected 95%CI suggested that these associations were not robust. The overall apparent prevalence of BoHV-1 exposure for culled cattle in Ireland declined in 2020 relative to 2018 (from 23.32 to 17.61%). Herd-size and the movement of animals were found to be important factors associated with animal-level risk, but there was less statistical support for sex-based or BVDV status associations.


Assuntos
Coinfecção , Herpesvirus Bovino 1 , Infecções por Pestivirus , Animais , Bovinos , Irlanda/epidemiologia , Estudos Soroepidemiológicos , Fatores de Risco , Diarreia
11.
Prev Vet Med ; 224: 106116, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38271923

RESUMO

There is sufficient evidence that both bovine herpesvirus (BoHV-1) and bubaline herpesvirus (BuHV-1) can overcome the species barrier represented by their respective hosts, cattle and buffalo. Although several studies have focused on the impact of BoHV-1 on buffalo, little is known about the impact of BuHV-1 on cattle. In this work, we evaluated the seroprevalence of BuHV-1 in the cattle population in an area where intensive buffalo farming is highly developed (Campania region, Italy). BuHV-1 seroprevalence of cattle sampled in this study was estimated to be 21.4% using a specific commercial ELISA for the detection of antibodies against glycoprotein E of the virus. Risk factor assessment by univariate analysis revealed a correlation between housing type and higher prevalence. Similarly, cattle housed with buffalo and adult animals had a higher likelihood of being seropositive. BoHV-1 vaccination did not prove to be a protective factor against BuHV-1 exposure. The role of age, grazing, and co-living with buffalo in influencing BuHV-1 exposure was also confirmed by multivariate analysis. All BuHV-1 positive animals were also tested with cross-serum neutralization aimed at evaluating the specific antibody titers against BoHV-1 and BuHV-1. We, therefore, assessed the potential cross-reaction between BoHV-1 and BuHV-1, the co-infection rate, and the agreement of the assays used. This study described the presence of BuHV-1 in the cattle population of the Campania region (Italy) and indicated the requirement to take BuHV-1 into consideration for any measures and control and/or eradication plans to be applied against BoHV-1.


Assuntos
Bison , Doenças dos Bovinos , Infecções por Herpesviridae , Herpesviridae , Herpesvirus Bovino 1 , Animais , Bovinos , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/veterinária , Búfalos , Estudos Soroepidemiológicos , Doenças dos Bovinos/epidemiologia , Anticorpos Antivirais
12.
Proteins ; 92(5): 610-622, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38069558

RESUMO

Bovine herpesvirus type 1 (BoHV-1) is a pathogen of cattle responsible for infectious bovine rhinotracheitis. The BoHV-1 UL49.5 is a transmembrane protein that binds to the transporter associated with antigen processing (TAP) and downregulates cell surface expression of the antigenic peptide complexes with the major histocompatibility complex class I (MHC-I). KLHDC3 is a kelch domain-containing protein 3 and a substrate receptor of a cullin2-RING (CRL2) E3 ubiquitin ligase. Recently, it has been identified that CRL2KLHDC3 is responsible for UL49.5-triggered TAP degradation via a C-degron pathway and the presence of the degron sequence does not lead to the degradation of UL49.5 itself. The molecular modeling of KLHDC3 in complexes with four UL49.5 C-terminal decapeptides (one native protein and three mutants) revealed their activity to be closely correlated with the conformation which they adopt in KLHDC3 binding cleft. To analyze the interaction between UL49.5 and KLHDC3 in detail, in this work a total of 3.6 µs long molecular dynamics simulations have been performed. The complete UL49.5-KLHDC3 complexes were embedded into the fully hydrated all-atom lipid membrane model with explicit water molecules. The network of polar interactions has been proposed to be responsible for the recognition and binding of the degron in KLHDC3. The interaction network within the binding pocket appeared to be very similar between two CRL2 substrate receptors: KLHDC3 and KLHDC2.


Assuntos
Herpesvirus Bovino 1 , Proteínas do Envelope Viral , Animais , Bovinos , Proteínas do Envelope Viral/química , Ligases/metabolismo , Ubiquitina/metabolismo , Degrons , Herpesvirus Bovino 1/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Ubiquitina-Proteína Ligases
13.
J Virol ; 98(1): e0143623, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38084958

RESUMO

Bovine alphaherpesvirus 1 (BoHV-1) infections cause respiratory tract disorders and suppress immune responses, which can culminate in bacterial pneumonia. Following acute infection, BoHV-1 establishes lifelong latency in sensory neurons present in trigeminal ganglia (TG) and unknown cells in pharyngeal tonsil. Latently infected calves consistently reactivate from latency after an intravenous injection of the synthetic corticosteroid dexamethasone (DEX), which mimics the effects of stress. The immediate early transcription unit 1 (IEtu1) promoter drives expression of infected cell protein 0 (bICP0) and bICP4, two key viral transcriptional regulators. The IEtu1 promoter contains two functional glucocorticoid receptor (GR) response elements (GREs), and this promoter is transactivated by GR, DEX, and certain Krüppel transcription factors that interact with GC-rich motifs, including consensus specificity protein 1 (Sp1) binding sites. Based on these observations, we hypothesized that Sp1 stimulates productive infection and transactivates key BoHV-1 promoters. DEX treatment of latently infected calves increased the number of Sp1+ TG neurons and cells in pharyngeal tonsil indicating that Sp1 expression is induced by stress. Silencing Sp1 protein expression with siRNA or mithramycin A, a drug that preferentially binds GC-rich DNA, significantly reduced BoHV-1 replication. Moreover, BoHV-1 infection of permissive cells increased Sp1 steady-state protein levels. In transient transfection studies, GR and Sp1 cooperatively transactivate IEtu1 promoter activity unless both GREs are mutated. Co-immunoprecipitation studies revealed that GR and Sp1 interact in mouse neuroblastoma cells (Neuro-2A) suggesting this interaction stimulates IEtu1 promoter activity. Collectively, these studies suggested that the cellular transcription factor Sp1 enhances productive infection and stress-induced BoHV-1 reactivation from latency.IMPORTANCEFollowing acute infection, bovine alphaherpesvirus 1 (BoHV-1) establishes lifelong latency in sensory neurons in trigeminal ganglia (TG) and pharyngeal tonsil. The synthetic corticosteroid dexamethasone consistently induces BoHV-1 reactivation from latency. The number of TG neurons and cells in pharyngeal tonsil expressing the cellular transcription factor specificity protein 1 (Sp1) protein increases during early stages of dexamethasone-induced reactivation from latency. Silencing Sp1 expression impairs BoHV-1 replication in permissive cells. Interestingly, mithramycin A, a neuroprotective antibiotic that preferentially binds GC-rich DNA, impairs Sp1 functions and reduces BoHV-1 replication suggesting that it is a potential antiviral drug. The glucocorticoid receptor (GR) and Sp1 cooperatively transactivate the BoHV-1 immediate early transcript unit 1 (IEtu1) promoter, which drives expression of infected cell protein 0 (bICP0) and bICP4. Mithramycin A also reduced Sp1- and GR-mediated transactivation of the IEtu1 promoter. These studies revealed that GR and Sp1 trigger viral gene expression and replication following stressful stimuli.


Assuntos
Infecções por Herpesviridae , Herpesvirus Bovino 1 , Receptores de Glucocorticoides , Fator de Transcrição Sp1 , Animais , Bovinos , Camundongos , Corticosteroides/metabolismo , Dexametasona/farmacologia , DNA/metabolismo , Herpesvirus Bovino 1/fisiologia , Plicamicina/análogos & derivados , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Virais/metabolismo , Fator de Transcrição Sp1/metabolismo
14.
Vet Microbiol ; 288: 109932, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043447

RESUMO

Bovine herpesvirus 1(BoHV-1) is an important bovine pathogen that causes great economic loss to cattle farms worldwide. The virus-productive infection in bovine kidney (MDBK) cells results in ATP depletion. The mechanisms are not well understood. Mitochondrial fatty acid ß-oxidation (FAO) is an important energy source in many tissues with high energy demand. Since carnitine palmitoyl-transferase 1 A (CPT1A) is the rate-limiting enzyme of FAO, we investigated the interactions between virus-productive infection and CPT1A signaling. Here, we found that virus-productive infection at the later stage significantly decreased CPT1A protein levels in all the detected cells, including MDBK, A549, and Neuro-2A cells, differentially altered the accumulation of CPT1A proteins in the nucleus and cytosol, and re-localized the protein in the nucleus. Etomoxir (ETO), an irreversible inhibitor of CPT1A, inhibited viral replication and partially interfered with the ability of BoHV-1 to alter CPT1A accumulation in the nucleus but not in the cytosol. Furthermore, ETO consistently reduced RNA levels of two viral regulatory proteins (bICP0 and bICP22) and protein expression of virion-associated proteins during productive infection, further supporting the important roles of CPT1A signaling in BoHV-1 productive infection. These data, for the first time, suggest that CPT1A is potentially involved in BoHV-1 productive infection.


Assuntos
Doenças dos Bovinos , Infecções por Herpesviridae , Herpesvirus Bovino 1 , Bovinos , Animais , Herpesvirus Bovino 1/genética , Replicação Viral , Infecções por Herpesviridae/veterinária , Transferases/metabolismo , Carnitina/metabolismo
15.
Vet Microbiol ; 287: 109899, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37931576

RESUMO

Bovine herpesvirus-1 (BoHV-1) can infect all breeds of cattle and cause respiratory and genital tract diseases. In the process of viral infection, viruses can use their own proteins to suppress the innate immunity of the host and promote its replication; however, the mechanism by which BoHV-1 evades the innate immune response is not fully understood. In this study, we found that rabbits inoculated with the live gene deletion vaccine BoHV-1-△gI/gE/TK generated higher interferon-ß (IFN-ß) production in the serum, liver, lung and kidney than rabbits inoculated with wt BoHV-1, which led to milder lesions in the lung and kidney. We performed gene deletion and ectopic expression experiments on viral proteins and found that gE was the major protein that inhibited IFN-ß expression. Further studies showed that MAVS and IRF3 were the targets of gE, and the specific mechanism was that gE inhibited IFN-ß production by promoting MAVS ubiquitination and interfering with the interaction between IRF3 and CBP/p300. These results suggest a new way of BoHV-1 inhibition of IFN-ß production to evade the host innate immunity.


Assuntos
Herpesvirus Bovino 1 , Bovinos , Coelhos , Animais , Herpesvirus Bovino 1/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Ubiquitinação , Interferon beta/genética , Interferon beta/metabolismo , Imunidade Inata
16.
J Gen Virol ; 104(11)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37976092

RESUMO

Virus vectored vaccines are not available commercially for cattle even though compelling potential applications exist. Bovine papular stomatitis virus (BPSV), a highly prevalent parapoxvirus, causes self-limited oral lesions in cattle. Ability of virus to accommodate large amounts of foreign DNA, induce low level of antiviral immunity, and circulate and likely persist in cattle populations, make BPSV an attractive candidate viral vector. Here, recombinant BPSV were constructed expressing either Bovine herpesvirus 1 (BoHV-1) glycoprotein gD (BPSVgD), or gD and gB (BPSVgD/gB). Immunization of BPSV serologically-positive calves with BPSVgD or BPSVgD/gB induced BoHV-1 neutralization antibodies and provided protection for three of four animals following a high dose BoHV-1 challenge at day 70 pi. Results indicate BPSV suitability as a candidate virus vector for cattle vaccines.


Assuntos
Doenças dos Bovinos , Herpesvirus Bovino 1 , Parapoxvirus , Estomatite , Vacinas , Vacinas Virais , Bovinos , Animais , Parapoxvirus/genética , Anticorpos Antivirais , Herpesvirus Bovino 1/genética , Vacinas Virais/genética , Doenças dos Bovinos/prevenção & controle
17.
Biologicals ; 84: 101720, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37944302

RESUMO

Bovine herpes virus-1 (BoHV-1) is responsible for production losses through decreased milk yields, abortions, infertility, and trade restrictions in the bovine population. The disease is endemic in many countries including India. As the virus harbors a unique feature of latency animals once infected with the virus remain sero-positive for lifetime and can re-excrete the virus when exposed to stressful conditions. Hence, identification and culling of infected animals is only the means to minimize infection-associated losses. In this study, an economical indigenous assay for the detection of BoHV-1 specific antibodies was developed to cater to the huge bovine population of the country. The viral structural gD protein, expressed in the prokaryotic system was used for optimization of an indirect ELISA for bovines followed by statistical validation of the assay. The diagnostic sensitivity and specificity of the indirect ELISA were 82.9% and 91.3% respectively. Systematically collected serum samples representing organized, unorganized and breeding farms of India were tested with the indigenously developed assay for further validation.


Assuntos
Doenças dos Bovinos , Herpesvirus Bovino 1 , Animais , Bovinos , Proteínas Virais , Ensaio de Imunoadsorção Enzimática , Anticorpos Antivirais , Índia , Doenças dos Bovinos/diagnóstico
18.
Sci Rep ; 13(1): 18659, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907654

RESUMO

Enzootic bovine leukosis virus (BLV) and bovine herpesvirus 1 (BHV-1) are very important infectious agents for the livestock industry worldwide. The present study aimed to explore the association between natural exposure to BLV and BHV-1 with sperm quality analyzed by Computer-Assisted Semen Analysis (CASA) systems. Ten sexually mature Brahman bulls, with sanitary status BLV+/BHV-1+ (n = 2), BLV-/BHV-1+ (n = 6) and BLV-/BHV-1- (n = 2) were evaluated twice, 30 days apart. Results showed that sanitary status of each bull was not associated with semen quality. It was found that the quality of the semen from the second collection was better due to the interruption of sexual rest. The evidence thus revealed that a bull infected with BLV generated good-quality contaminated semen and, therefore, that it is essential to detect contaminated seminal samples to prevent the spread of BLV. A multivariate analysis showed the presence of four sperm subpopulations in Brahman bulls that differ significantly in their kinematic patterns and with respect to sanitary status (P < 0.05), indicating that infection-free and seronegative bulls present the best kinematic parameters, which improved discrimination of sperm quality according to sanitary status. Overall, the analyses indicate that the seropositive-infected bulls with BLV and BHV-1 should be excluded from beef cattle farms.


Assuntos
Doenças dos Bovinos , Herpesvirus Bovino 1 , Vírus da Leucemia Bovina , Masculino , Animais , Bovinos , Análise do Sêmen , Sêmen
19.
Vet Ital ; 59(1): 65-70, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37994637

RESUMO

Infectious bovine rhinotracheitis (IBR) is a highly communicable disease of cattle and wild ruminants that is caused by Bovine alphaherpesvirus 1 (BoHV­1). For IBR control, several developed countries have adopted the immunization and eradication programs focusing on IBR­positive animals. In Pakistan, livestock producers are importing commercially available vaccine of BoHV­1, but no studies on the efficacy of these commercial vaccines against local isolates are available. Therefore, the present study was aimed to evaluate the efficacy of a commercially available vaccine of BoHV­1 against local field isolates of virus. The rabbit model was used and the vaccine was evaluated for immunogenicity and protection after challenge with a highly virulent strain of a field virus. The immune response was measured by virus neutralization titers (VNT). This vaccine induced a humoral response in rabbits but that was not sufficient to completely protect the vaccinated animals against the wild­type BoHV­1 strain challenge. While a low virus titer compared to control rabbits was observed in the vaccinated rabbits (p<0.05), there was no sterilizing immunity or freedom from infection. However, complete freedom from disease, for example, the absence of pyrexia was noticed in the vaccinated group. In conclusion, the present study demonstrated that imported vaccine stock provoked only a partial protection against indigenous isolated of BoHV­1. However, tests performed on rabbits are preliminary, as only those performed on the source species can determine more reliable results.


Assuntos
Doenças dos Bovinos , Herpesvirus Bovino 1 , Rinotraqueíte Infecciosa Bovina , Vacinas Virais , Bovinos , Animais , Coelhos , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Paquistão , Vacinação/veterinária , Anticorpos Antivirais
20.
Viruses ; 15(10)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37896756

RESUMO

Bovine herpesvirus type 1 (BoHV-1) is an important agricultural pathogen that infects cattle and other ruminants worldwide. Though it was first sequenced and annotated over twenty years ago, the Cooper strain, used in this study, was sequenced as recently as 2012 and is currently said to encode 72 unique proteins. However, tandem mass spectrometry has identified several peptides produced during active infection that align with the BoHV-1 genome in unannotated regions. One of these abundant peptides, "ORF M", aligned antisense to the DNA helicase/primase protein UL5. This study characterizes the novel transcript and its protein product and provides evidence to support the existence of homolog protein-coding genes in other Herpesviruses.


Assuntos
Infecções por Herpesviridae , Herpesvirus Bovino 1 , Animais , Bovinos , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/metabolismo , Sequência de Bases , Simplexvirus/genética , DNA Primase/genética , Peptídeos/genética
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