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1.
BMC Genomics ; 25(1): 534, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816794

RESUMO

BACKGROUND: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology. RESULT: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4+ and CD8+ T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs. CONCLUSION: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts.


Assuntos
Pulmão , Vírus Visna-Maedi , Animais , Vírus Visna-Maedi/genética , Pulmão/virologia , Pulmão/imunologia , Pulmão/patologia , Ovinos , Perfilação da Expressão Gênica , Transcriptoma , Pneumonia Intersticial Progressiva dos Ovinos/genética , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Mapas de Interação de Proteínas , Regulação da Expressão Gênica , Ontologia Genética
2.
Int J Mol Sci ; 22(18)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34575988

RESUMO

Maedi-Visna-like genotype A strains and Caprine arthritis encephaltis-like genotype B strains are small ruminant lentiviruses (SRLV) which, for incompletely understood reasons, appear to be more virulent in sheep and goats, respectively. A 9-month in vivo infection experiment using Belgian genotype A and B SRLV strains showed that almost all homologous (genotype A in sheep; genotype B in goats) and heterologous (genotype A in goats; genotype B in sheep) intratracheal inoculations resulted in productive infection. No differences in viremia and time to seroconversion were observed between homologous and heterologous infections. Higher viral loads and more severe lesions in the mammary gland and lung were however detected at 9 months post homologous compared to heterologous infection which coincided with strongly increased IFN-γ mRNA expression levels upon homologous infection. Pepscan analysis revealed a strong antibody response against immune-dominant regions of the capsid and surface proteins upon homologous infection, which was absent after heterologous infection. These results inversely correlated with protection against virus replication in target organs and observed histopathological lesions, and thus require an in-depth evaluation of a potential role of antibody dependent enhancement in SRLV infection. Finally, no horizontal intra- and cross-species SRLV transmission to contact animals was detected.


Assuntos
Vírus da Artrite-Encefalite Caprina/fisiologia , Genótipo , Doenças das Cabras/imunologia , Cabras , Imunidade Humoral , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Ovinos , Replicação Viral/imunologia , Vírus Visna-Maedi/fisiologia , Animais , Anticorpos Antivirais/imunologia , Feminino , Doenças das Cabras/genética , Doenças das Cabras/patologia , Doenças das Cabras/virologia , Cabras/imunologia , Cabras/virologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/patologia , Glândulas Mamárias Animais/virologia , Pneumonia Intersticial Progressiva dos Ovinos/genética , Pneumonia Intersticial Progressiva dos Ovinos/patologia , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Ovinos/imunologia , Ovinos/virologia , Especificidade da Espécie , Carga Viral/imunologia
3.
PLoS One ; 15(9): e0238781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32911525

RESUMO

Maedi-visna (MV) is a complex lentiviral disease syndrome characterised by long immunological and clinical latencies and chronic progressive inflammatory pathology. Incurable at the individual level, it is widespread in most sheep-keeping countries, and is a cause of lost production and poor animal welfare. Culling seropositive animals is the main means of control, but it might be possible to manage virus transmission effectively if its epidemiology was better quantified. We derive a mathematical epidemiological model of the temporal distributions of seroconversion probabilities and estimate susceptibility, transmission rate and latencies in three serological datasets. We demonstrate the existence of epidemiological latency, which has not explicitly been recognised in the SRLV literaure. This time delay between infection and infectiousness apparently exceeds the delay between infection and seroconversion. Poor body condition was associated with more rapid seroconversion, but not with a higher probability of infection. We estimate transmission rates amongst housed sheep to be at about 1,000 times faster than when sheep were at grass, when transmission was negligible. Maternal transmission has only a small role in transmission, because lambs from infected ewes have a low probability of being infected directly by them, and only a small proportion of lambs need be retained to maintain flock size. Our results show that MV is overwhelmingly a disease of housing, where sheep are kept in close proximity. Prevalence of MV is likely to double each year from an initial low incidence in housed flocks penned in typically-sized groups of sheep (c. 50) for even a few days per year. Ewes kept entirely at grass are unlikely to experience transmission frequently enough for MV to persist, and pre-existing infection should die out as older ewes are replaced, thereby essentially curing the flock.


Assuntos
Pneumonia Intersticial Progressiva dos Ovinos/transmissão , Vírus Visna-Maedi/patogenicidade , Animais , Monitoramento Epidemiológico/veterinária , Incidência , Modelos Teóricos , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Prevalência , Soroconversão , Ovinos/imunologia , Ovinos/virologia , Doenças dos Ovinos/epidemiologia , Vírus Visna-Maedi/imunologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-29127994

RESUMO

Maedi-visna virus (MVV), a lentivirus of sheep, shares with other lentiviruses the ability to establish a lifelong infection. In this study five sheep were infected intravenously with MVV and housed together with a number of uninfected sheep for natural transmission. All virus isolates from ten sheep that had been infected naturally had multiple mutations in the principal neutralization domain in Env and were antigenic variants, while three of four isolates from the carrier sheep had identical sequences to the infecting strain and were not antigenic variants. There was evidence of positive selection in the gene, particularly in amino acids comprising the neutralization epitope and some adjacent glycosylation sites. Together these results suggest that virus persistence is acquired by a reservoir of latent viruses, and that there is selection for antigenic variants of virus that is transmitted naturally.


Assuntos
Pneumonia Intersticial Progressiva dos Ovinos/virologia , Vírus Visna-Maedi , Animais , Variação Antigênica/genética , Variação Antigênica/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Masculino , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Reação em Cadeia da Polimerase/veterinária , Ovinos/virologia , Latência Viral , Vírus Visna-Maedi/genética , Vírus Visna-Maedi/imunologia , Vírus Visna-Maedi/fisiologia
5.
Comp Immunol Microbiol Infect Dis ; 36(4): 405-13, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23582860

RESUMO

Visna/Maedi virus (VMV) is a lentivirus that infects cells of the monocyte/macrophage lineage in sheep. Infection with VMV may lead to Visna/Maedi (VM) disease, which causes a multisystemic inflammatory disorder causing pneumonia, encephalitis, mastitis and arthritis. The role of ovine immune response genes in the development of VM disease is not fully understood. In this work, sheep of the Rasa Aragonesa breed were divided into two groups depending on the presence/absence of VM-characteristic clinical lesions in the aforementioned organs and the relative levels of candidate gene expression, including cytokines and innate immunity loci were measured by qPCR in the lung and udder. Sheep with lung lesions showed differential expression in five target genes: CCR5, TLR7, and TLR8 were up regulated and IL2 and TNFα down regulated. TNFα up regulation was detected in the udder.


Assuntos
Regulação Viral da Expressão Gênica/imunologia , Pulmão/virologia , Glândulas Mamárias Animais/virologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Vírus Visna-Maedi/imunologia , Animais , Feminino , Perfilação da Expressão Gênica/veterinária , Modelos Lineares , Pulmão/imunologia , Glândulas Mamárias Animais/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/virologia , RNA Viral/química , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Ovinos , Vírus Visna-Maedi/genética
6.
Vet Immunol Immunopathol ; 152(3-4): 277-88, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23375019

RESUMO

A single broadly reactive standard ELISA is commonly applied to control small ruminant lentivirus (SRLV) spread, but type specific ELISA strategies are gaining interest in areas with highly prevalent and heterogeneous SRLV infections. Short (15-residue) synthetic peptides (n=60) were designed in this study using deduced amino acid sequence profiles of SRLV circulating in sheep from North Central Spain and SRLV described previously. The corresponding ELISAs and two standard ELISAs were employed to analyze sera from sheep flocks either controlled or infected with different SRLV genotypes. Two outbreaks, showing SRLV-induced arthritis (genotype B2) and encephalitis (genotype A), were represented among the infected flocks. The ELISA results revealed that none of the assays detected all the infected animals in the global population analyzed, the assay performance varying according to the genetic type of the strain circulating in the area and the test antigen. Five of the six highly reactive (57-62%) single peptide ELISAs were further assessed, revealing that the ELISA based on peptide 98M (type A ENV-SU5, consensus from the neurological outbreak) detected positives in the majority of the type-A specific sera tested (Se: 86%; Sp: 98%) and not in the arthritic type B outbreak. ENV-TM ELISAs based on peptides 126M1 (Se: 82%; Sp: 95%) and 126M2 0,65 0.77 (Se: 68%; Sp: 88%) detected preferentially caprine arthritis encephalitis (CAEV, type B) and visna/maedi (VMV, type A) virus infections respectively, which may help to perform a preliminary CAEV vs. VMV-like typing of the flock. The use of particular peptide ELISAs and standard tests individually or combined may be useful in the different areas under study, to determine disease progression, diagnose/type infection and prevent its spread.


Assuntos
Ensaio de Imunoadsorção Enzimática/veterinária , Infecções por Lentivirus/veterinária , Doenças dos Ovinos/diagnóstico , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Vírus da Artrite-Encefalite Caprina/genética , Vírus da Artrite-Encefalite Caprina/imunologia , Surtos de Doenças/veterinária , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Genes gag , Cabras , Infecções por Lentivirus/diagnóstico , Infecções por Lentivirus/epidemiologia , Dados de Sequência Molecular , Filogenia , Pneumonia Intersticial Progressiva dos Ovinos/diagnóstico , Pneumonia Intersticial Progressiva dos Ovinos/epidemiologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/imunologia , Carneiro Doméstico , Espanha/epidemiologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Visna/diagnóstico , Visna/epidemiologia , Visna/imunologia , Vírus Visna-Maedi/genética , Vírus Visna-Maedi/imunologia
7.
Comp Immunol Microbiol Infect Dis ; 35(3): 259-69, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22237012

RESUMO

The small ruminant lentiviruses include the prototype for the genus, visna-maedi virus (VMV) as well as caprine arthritis encephalitis virus (CAEV). Infection of sheep or goats with these viruses causes slow, progressive, inflammatory pathology in many tissues, but the most common clinical signs result from pathology in the lung, mammary gland, central nervous system and joints. This review examines replication, immunity to and pathogenesis of these viruses and highlights major differences from and similarities to some of the other lentiviruses.


Assuntos
Vírus da Artrite-Encefalite Caprina/patogenicidade , Infecções por Lentivirus/veterinária , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Ruminantes/virologia , Vírus Visna-Maedi/patogenicidade , Animais , Antígenos Virais/imunologia , Vírus da Artrite-Encefalite Caprina/imunologia , Vírus da Artrite-Encefalite Caprina/fisiologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Imunidade Celular , Infecções por Lentivirus/imunologia , Infecções por Lentivirus/virologia , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/virologia , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Ruminantes/imunologia , Ovinos/imunologia , Ovinos/virologia , Vacinação/veterinária , Replicação Viral , Vírus Visna-Maedi/imunologia , Vírus Visna-Maedi/fisiologia
8.
Vet Immunol Immunopathol ; 145(1-2): 438-46, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22244517

RESUMO

Maedi-Visna (MV) and ovine pulmonary adenocarcinoma (OPA) are two retroviral diseases occurring worldwide that affect adult sheep. Differences in incidence, which may be related to sheep-rearing and housing choices, as well as to genetics, and disease progression have been reported for both diseases. In this work four microsatellites located in immune-relevant regions, the major histocompatibility complex (MHC) region, interferon-γ and interleukin-12p35, were genotyped to determine their association with disease progression. The analysed sample included Latxa sheep with and without OPA and MV-characteristic lesions in their lungs. The microsatellites in the MHC were the most diverse, while the ones located in the cytokines were the less polymorphic. In the case of IFN-γ the results suggested the presence of null alleles. Significant results were detected for several microsatellite alleles in the association analysis carried out by logistic regression. All statistical analyses included a flock effect adjustment to avoid false positives due to genetic structuration. MHC Class I microsatellite alleles OMHC1*205 and OMHC1*193 were associated with disease progression for Maedi and OPA, respectively. Moreover, MHC Class II microsatellite allele DRB2*275 was associated with presence of lesions in Maedi. Furthermore, the MHC microsatellites were combined for a bioinformatic haplotype inference with the PHASE software. In total, 73 haplotypes were detected, 18 of them in more than 6 animals. After standard and weighted logistic regression analysis, two of them were significantly associated with susceptibility: OMHC1*205-DRB2*271 for Maedi and OMHC1*193-DRB2*271 for OPA, both with the Class I microsatellite alleles associated in the marker by marker study. Although more extensive analyses are needed to disentangle the relationship between host genetics and disease, as far as we know this is the first study demonstrating a significant association between sheep MHC Class I microsatellite alleles and susceptibility to Maedi-Visna and OPA viral diseases.


Assuntos
Complexo Principal de Histocompatibilidade/genética , Repetições de Microssatélites/genética , Pneumonia Intersticial Progressiva dos Ovinos/genética , Adenomatose Pulmonar Ovina/genética , Vírus Visna-Maedi , Alelos , Animais , Frequência do Gene/genética , Genes MHC Classe I/genética , Genes MHC Classe I/imunologia , Genes MHC da Classe II/genética , Genes MHC da Classe II/imunologia , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Repetições de Microssatélites/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Adenomatose Pulmonar Ovina/imunologia , Ovinos/genética , Ovinos/imunologia
9.
J Comp Pathol ; 147(1): 1-10, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22000038

RESUMO

This study investigates the nervous form of ovine maedi-visna by histological and immunohistochemical techniques. The aim was to study the lesion types and the local cellular immune response related to each lesion type, and the possible relationship between these parameters. Thirty-four Assaf ewes were studied, 29 of which had shown nervous signs. Microscopical lesion patterns were described according to location, extent and predominance of inflammatory cell type. Immunohistochemical labelling of T cells (CD3(+), CD4(+), CD8(+) and cells expressing the γδ form of the T-cell receptor), B cells and macrophages revealed clear differences between the lesion patterns. Two main lesion types were described. Lymphocytic lesions had areas of mild-moderate injury characterized by a predominance of infiltrating T cells. Histiocytic lesions were more severe and had extensive areas of malacia and dominant infiltration by macrophages and B cells. Each animal had a unique lesion pattern and these differences could be due to individual resistance to the progression of infection. The lymphocytic lesions appear to represent initial or latent phases of slow progression, in which the animal presents some natural resistance to the infection. The histiocytic pattern may reflect a poor immune response or a greater virulence of the viral strain.


Assuntos
Interações Hospedeiro-Patógeno , Imunidade Celular/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/patologia , Vírus Visna-Maedi/imunologia , Animais , Antígenos CD/metabolismo , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores/metabolismo , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Plexo Corióideo/imunologia , Plexo Corióideo/metabolismo , Plexo Corióideo/patologia , Progressão da Doença , Feminino , Histiócitos/metabolismo , Histiócitos/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Meninges/imunologia , Meninges/metabolismo , Meninges/patologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Ovinos , Linfócitos T/metabolismo , Linfócitos T/patologia , Vírus Visna-Maedi/isolamento & purificação , Vírus Visna-Maedi/patogenicidade
10.
Vet Res ; 42: 28, 2011 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-21314911

RESUMO

This study aims to characterize the mannose receptor (MR) gene in sheep and its role in ovine visna/maedi virus (VMV) infection. The deduced amino acid sequence of ovine MR was compatible with a transmembrane protein having a cysteine-rich ricin-type amino-terminal region, a fibronectin type II repeat, eight tandem C-type lectin carbohydrate-recognition domains (CRD), a transmembrane region, and a cytoplasmic carboxy-terminal tail. The ovine and bovine MR sequences were closer to each other compared to human or swine MR. Concanavalin A (ConA) inhibited VMV productive infection, which was restored by mannan totally in ovine skin fibroblasts (OSF) and partially in blood monocyte-derived macrophages (BMDM), suggesting the involvement of mannosylated residues of the VMV ENV protein in the process. ConA impaired also syncytium formation in OSF transfected with an ENV-encoding pN3-plasmid. MR transcripts were found in two common SRLV targets, BMDM and synovial membrane (GSM) cells, but not in OSF. Viral infection of BMDM and especially GSM cells was inhibited by mannan, strongly suggesting that in these cells the MR is an important route of infection involving VMV Env mannosylated residues. Thus, at least three patterns of viral entry into SRLV-target cells can be proposed, involving mainly MR in GSM cells (target in SRLV-induced arthritis), MR in addition to an alternative route in BMDM (target in SRLV infections), and an alternative route excluding MR in OSF (target in cell culture). Different routes of SRLV infection may thus coexist related to the involvement of MR differential expression.


Assuntos
Concanavalina A/farmacologia , Células Gigantes/virologia , Lectinas Tipo C/genética , Lectinas de Ligação a Manose/genética , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Receptores de Superfície Celular/genética , Vírus Visna-Maedi/fisiologia , Animais , Western Blotting/veterinária , Imuno-Histoquímica/veterinária , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Macrófagos/imunologia , Receptor de Manose , Lectinas de Ligação a Manose/química , Lectinas de Ligação a Manose/metabolismo , Dados de Sequência Molecular , Pneumonia Intersticial Progressiva dos Ovinos/metabolismo , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Receptores Virais/química , Receptores Virais/genética , Receptores Virais/metabolismo , Análise de Sequência de Proteína/veterinária , Ovinos
11.
Dev Comp Immunol ; 35(2): 182-92, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20875448

RESUMO

One of the major roles of innate immunity system is the recognition and the determination of the nature of the antigen. This ability is encompassed by specific receptors as Toll-like receptors (TLRs). TLR9 recognizes bacterial and viral CpG motifs, while their potent immunostimulation effect seems to be promising for lentiviral therapies. Recent studies, however, show the presence of a big polymorphism within the TLR genes and the linkage between substitutions and susceptibility to various infections. Moreover, different recognition ability seems to be utilized by different species and possibly breeds. In this study, we characterized the protein coding region of ovine TLR9 gene. By using comparative analysis of two closely related species and humans, we suggest, which characteristics of protein could be responsible for altered recognition. Furthermore, analyzing the presence of the substitutions, we show the intraspecies polymorphism and its possible implications, while attempting to define the association of discovered substitutions with the maedi visna infection.


Assuntos
Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Polimorfismo de Nucleotídeo Único , Ovinos , Receptor Toll-Like 9/química , Receptor Toll-Like 9/genética , Visna/imunologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Ilhas de CpG , Humanos , Imunidade Inata , Leucina/genética , Dados de Sequência Molecular , Mutação , Fases de Leitura Aberta , Pneumonia Intersticial Progressiva dos Ovinos/genética , Estrutura Secundária de Proteína , Sequências Repetitivas de Aminoácidos , Ovinos/genética , Ovinos/metabolismo , Ovinos/virologia , Visna/genética , Vírus Visna-Maedi
12.
Vet Immunol Immunopathol ; 138(1-2): 51-9, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20638136

RESUMO

Toll-like receptors (TLRs) 2, 3, 4, 7, 8 and 9 play a crucial role in the recognition of viral entities and modulation of the innate immune system. This work presents sequence analysis of ovine TLR7 and TLR8 genes, depicts novel mutations and describes frequencies of mutations in Maedi Visna infected and healthy sheep. Totally 48 samples of the breed Tsigai were analyzed for the presence of mutations. Within 20 mutations, 14 were silent whereas 6 were missense. The frequencies of missense mutations in the Maedi Visna infected compared to non-infected sheep were: Lys115Glu (P-0.766, F-test), Asn117 (P-0.380) and Lys818Arg (P-0.739). These three mutations were localized in extra LRR (lucine rich repeat) region of TLR7, while mutation Ile73Leu (P-0.498) was located within LRR2 motif. Both mutations in TLR8, Asn165Lys (P-1.0) and Tyr349His (P-0.700), were present in extra LRR region. The secondary structure analysis of ovine TLR7 and TLR8 revealed conserved LRR motif structure, however with some irregularities compared to cattle and human. Transmembrane domains of TLR7 and TLR8 showed 100% homology between sheep and cattle wherein no mutations were found. In both TLRs TIR domains were highly conserved with occurrence of 4 silent mutations. Mutations in TLR7 and TLR8 may play an important role as predisposition factor for Maedi Visna infection. Considering the sequence homology among sheep, cattle and human genes encoding TLR7 and TLR8, we predict their similar function, localization and downstream signaling.


Assuntos
Mutação , Pneumonia Intersticial Progressiva dos Ovinos/genética , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Ovinos/genética , Ovinos/imunologia , Receptor 7 Toll-Like/genética , Receptor 8 Toll-Like/genética , Visna/genética , Visna/imunologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sequência de Bases , Bovinos , Análise Mutacional de DNA , Primers do DNA/genética , Feminino , Predisposição Genética para Doença , Humanos , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Mutação Puntual , Estrutura Secundária de Proteína , Sequências Repetitivas de Aminoácidos , Homologia de Sequência de Aminoácidos , Receptor 7 Toll-Like/química , Receptor 8 Toll-Like/química
13.
Immunogenetics ; 62(2): 75-83, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20049428

RESUMO

Ovine pulmonary adenocarcinoma (OPA) and Maedi-Visna (Maedi) are two chronic respiratory diseases of retroviral origin which occur worldwide. It is known that different host genetic factors influence the outcome of viral infections. To determine if variation in the Mhc-DRB1 gene was associated with progression to these ovine diseases, sheep lungs with and without OPA and Maedi lesions were collected. A sequence-based method was applied and 40 different alleles were detected in the sample analysed. In the allele-by-allele association analysis, allele DRB1*0325 had a significant association with susceptibility to Maedi (P = 0.045). For OPA, DRB1*0143 and DRB1*0323 were significantly associated with susceptibility (P = 0.024 and P = 0.029), and allele DRB1*0702 was significantly associated with resistance (P = 0.012). Based on these results, the Mhc-DRB1 alleles were classified by effect in three categories-susceptible (S), resistant (R) and neutral (N)-and animals were reassigned the genotypes as S/S, S/R, S/N, R/R, R/N and N/N. In a second analysis, penalised logistic regression models including a flock effect were run. In Maedi, significant association was detected for the N/S heterozygote (P = 0.0007), but not for the S/S homozygote, probably as a result of the low number of S/S animals. In OPA, association was detected for both the S/S and R/R homozygotes (P = 0.005 and P = 0.047). This allele grouping method may be applied in association studies with highly variable genes. This is the first study demonstrating significant associations between sheep Mhc-DRB1 alleles and susceptibility to OPA and Maedi. Therefore, both diseases are suitable candidates for more comprehensive genetic studies.


Assuntos
Genes MHC da Classe II , Predisposição Genética para Doença , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Adenomatose Pulmonar Ovina/imunologia , Animais , Pneumonia Intersticial Progressiva dos Ovinos/genética , Polimorfismo Genético , Adenomatose Pulmonar Ovina/genética , Ovinos , Vírus Visna-Maedi/imunologia
14.
Clin Vaccine Immunol ; 16(4): 551-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19261772

RESUMO

Studies were undertaken to determine whether anti-ovine progressive pneumonia virus (OPPV) antibody responses in serum or OPP provirus levels in peripheral blood associate with the degree of histologically measured tissue lesions in naturally OPPV-infected sheep. Sections of formalin-fixed, paraffin-embedded, and hematoxylin- and eosin-stained lung, mammary gland, carpal synovial membrane, and brain tissues from 11 OPPV-infected ewes (mean age of 8.6 years) and 5 OPPV-uninfected ewes (mean age of 6 years) were evaluated for lesion severity. Ovine progressive pneumonia (OPP) provirus levels and anti-OPPV antibody titers in peripheral blood and serum samples, respectively, were measured upon euthanasia and 3 years prior to euthanasia. Both mean peripheral OPP provirus levels and mean serum anti-surface envelope glycoprotein (anti-SU) antibody titers at the time of euthanasia were significantly higher in ewes with moderate to severe histological lesions than in ewes with no to mild histological lesions. However, although mean peripheral blood OPP provirus levels at euthanasia and 3 years prior to euthanasia significantly correlated with the highest histological lesion score for any affected tissue (two-tailed P values, 0.03 and 0.02), mean serum anti-SU antibody titers, anti-capsid antibody titers, and anti-transmembrane 90 antibody titers at euthanasia did not show a significant correlation with the highest histological lesion score for any tissue (two-tailed P values, 0.32, 0.97, and 0.18, respectively). These data are the first to show that OPP provirus levels predict and correlate with the extent of OPPV-related histological lesions in various OPPV-affected tissues. These findings suggest that peripheral OPP provirus levels quantitatively contribute more to the development of histological lesions than the systemic anti-SU antibody host immune response.


Assuntos
Pulmão/patologia , Pneumonia Intersticial Progressiva dos Ovinos/patologia , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Provírus/isolamento & purificação , Carga Viral , Vírus Visna-Maedi/isolamento & purificação , Animais , Anticorpos Antivirais/sangue , Encéfalo/patologia , Leucócitos/virologia , Glândulas Mamárias Animais/patologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Índice de Gravidade de Doença , Ovinos , Membrana Sinovial/patologia , Vírus Visna-Maedi/imunologia
15.
Immunogenetics ; 60(12): 749-58, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18797863

RESUMO

Previous studies initiated defining the role of host genetics in influencing the outcome of exposure to ovine progressive pneumonia virus. However, specific genes influencing host control of virus replication and disease progression have not been identified. This study, using 383 ewes of the Columbia, Polypay, and Rambouillet breeds, tested the hypothesis that host control of OPPV as measured by provirus levels in the peripheral blood associates with certain breeds and MHC class II Ovis aries (Ovar)-DRB1 expressed alleles. Rambouillet ewes were less likely to have measurable provirus levels as compared to Columbia ewes at ages 5 and 6 (P value < 0.02), and they exhibited lower provirus levels when compared to both Columbia and Polypay ewes of the same ages (P value < 0.05). The presence of DRB1*0403- or DRB1*07012-expressed alleles were significantly associated (P value = 0.019 and 0.0002, respectively) with lower OPP provirus levels but only were only found in 11% of the ewe flock. Analysis of each segregating amino acid in the beta1 domain of DR beta-chain revealed that amino acids Y31, T32, N37, T51, Q60, or N74 significantly associated (P value range = 0.0003-0.018) with lower OPP provirus levels, whereas amino acids H32, A38, or I67 associated (P value range = 0.013-0.043) with higher OPP provirus levels. These results suggest that Ovar-DRB1 contributes as one host genetic factor that controls OPP provirus levels, but does not fully account for the breed-specific OPP proviral differences.


Assuntos
Genes MHC da Classe II , Antígenos de Histocompatibilidade Classe II/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/genética , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Provírus/isolamento & purificação , Doenças dos Ovinos/genética , Doenças dos Ovinos/virologia , Ovinos/genética , Vírus Visna-Maedi/isolamento & purificação , Sequência de Aminoácidos , Animais , Sequência de Bases , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos/genética , Antígenos de Histocompatibilidade Classe II/genética , Interações Hospedeiro-Patógeno , Filogenia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Alinhamento de Sequência , Homologia de Sequência , Ovinos/imunologia , Doenças dos Ovinos/imunologia , Especificidade da Espécie , Carga Viral , Viremia/genética , Viremia/imunologia , Integração Viral , Replicação Viral
16.
J Gen Virol ; 89(Pt 3): 716-721, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18272763

RESUMO

We have shown previously that a type-specific neutralization domain is located within a 39 aa sequence in the fourth variable domain of gp135 in visna/maedi virus. We now show that neutralizing antibodies detected early in infection are directed to this epitope, suggesting an immunodominant nature of this domain. Ten antigenic variants were previously analysed for mutations in this region, and all but one were found to be mutated. To assess the importance of these mutations in replication and neutralization, we reconstructed several of the mutations in an infectious molecular clone and tested the resulting viruses for neutralization phenotype and replication. Mutation of a conserved cysteine was shown to alter the neutralization epitope, whilst the replication kinetics in macrophages were unchanged. Mutations modulating potential glycosylation sites were found in seven of the ten antigenic variants. A frequently occurring mutation, removing a potential glycosylation site, had no effect on its own on the neutralization phenotype of the virus. However, adding an extra potential glycosylation site in the region resulted in antigenic escape. The results indicate that the conserved cysteine plays a role in the structure of the epitope and that glycosylation may shield the principal neutralization site.


Assuntos
Anticorpos Antivirais/imunologia , Cisteína/química , Mutação , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vírus Visna-Maedi/genética , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/sangue , Linhagem Celular , Células Cultivadas , Plexo Corióideo/citologia , Plexo Corióideo/virologia , Glicosilação , Epitopos Imunodominantes/química , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Dados de Sequência Molecular , Testes de Neutralização , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Ovinos , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismo , Vírus Visna-Maedi/imunologia
17.
Vet Immunol Immunopathol ; 119(3-4): 222-32, 2007 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17624445

RESUMO

DNA vaccine candidates against Maedi-Visna virus (MVV) infection in ovines were developed as an alternative to conventional vaccines. Candidates were constructed by cloning genes encoding the MVV gag polyprotein and gag proteins p16 and p25 fused to a beta-galactosidase reporter in a plasmid backbone. Transfection of different ovine cells showed a higher protein expression with plasmid lacZp16, which was hence further optimised by (i) removing a putative inhibitory sequence via reduction of the AU-content in the p16 gene or by (ii) introducing a secretory signal (Sc) to promote antigen secretion and increase its presentation to APCs. Unexpectedly, plasmids constructed on the basis of the first strategy by mutagenesis of lacZp16 (lacZp16mut(24)), led to a reduction in the expression of the antigen/reporter fusion in cultured ovine cells. This indicates that the high AU content in MVV does not inhibit protein expression. However, mice primed with lacZp16mut(24) and boosted with MVV protein displayed higher humoral response when compared with control lacZp16. The addition of the Sc signal (Sc-p16) led to lower amounts of intracellular antigen/reporter fusion in transfected ovine cells, thus confirming secretion. These findings correlate with in vivo experiments, which showed that mice primed with Sc-p16 and boosted with MVV exhibited stronger antibody responses when compared with control mice primed with lacZp16 and boosted with MVV. Stronger humoral responses were recorded by immunising mice with (i) Sc-p16 and lacZp16mut(24) plasmids together or with (ii) one plasmid containing both the mutations and the Sc signal.


Assuntos
Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Ovinos/imunologia , Ovinos/virologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Vírus Visna-Maedi/imunologia , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Antígenos Virais/metabolismo , Células Cultivadas , Feminino , Genes Virais , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Intersticial Progressiva dos Ovinos/prevenção & controle , Fatores de Tempo
18.
Front Biosci ; 12: 1532-43, 2007 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17127400

RESUMO

The ovine maedi-visna virus (MVV) was the first lentivirus to be isolated and characterized 1957 in Iceland. MVV leads to a life-long, persistent infection with slow development of lesions in the lung and the central nervous system (CNS). The main target cells of MVV are of the monocyte/macrophage lineage and it does not infect T-lymphocytes or cause immune suppression like human immune deficiency virus (HIV). In spite of a fairly good immune response, including both neutralizing antibodies and cytotoxic T lymphocytes, the virus persists in the host and establishes a life-long infection. There are strong indications that the pathological lesions are immune-mediated and vaccination attempts have not only failed to induce sterile immunity but have occasionally caused increased viremia and more severe disease.


Assuntos
Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Vírus Visna-Maedi/imunologia , Visna/imunologia , Animais , Formação de Anticorpos , Imunidade Celular , Pneumonia Intersticial Progressiva dos Ovinos/prevenção & controle , Ovinos , Vacinas Virais , Visna/prevenção & controle
19.
Vet Immunol Immunopathol ; 113(3-4): 357-66, 2006 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-16876878

RESUMO

Antibody-dependent cell-mediated cytotoxicity (ADCC) specific for maedi visna virus (MVV) has never been described. The IgG antibody response to MVV is restricted to an IgG1 response whilst MVV specific IgG2 is never seen in persistently infected sheep. To determine whether the isotypic restriction of the antibody response is responsible for the lack of ADCC, an ADCC assay was developed using polyclonal serum raised to recombinant MVV ENV protein. Sheep immunised with a recombinant GST:SUenv fusion protein in complete Freund's adjuvant produced an antibody response which contained IgG1 and IgG2 antibodies. The activity of this serum in an ADCC assay was compared to serum from persistently infected sheep. Serum from immunised sheep mediated ADCC reactions whilst no activity was ever seen in persistently infected sheep serum. IgG2 may therefore be the possible effector isotype for ADCC reactions against MVV. Failure of the IgG2 dependent ADCC system in vivo may contribute to the persistence of MVV-infected macrophages in vivo.


Assuntos
Anticorpos Antivirais/imunologia , Imunoglobulina G/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Proteínas do Envelope Viral/imunologia , Vírus Visna-Maedi/imunologia , Animais , Citotoxicidade Celular Dependente de Anticorpos , Baculoviridae/genética , Western Blotting/veterinária , Portador Sadio/imunologia , Portador Sadio/veterinária , Portador Sadio/virologia , DNA Viral/química , DNA Viral/genética , Imunoglobulina G/sangue , Pneumonia Intersticial Progressiva dos Ovinos/sangue , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Ovinos , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Vírus Visna-Maedi/genética
20.
Res Vet Sci ; 80(2): 226-34, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16045950

RESUMO

A recent large-scale experimental study showed that bottle-feeding ovine colostrum from seropositive ewes results in high MVV-seroconversion in lambs. In contrast, relatively few lambs that naturally suckled colostrum from seropositive dams seroconverted as a result of it. Furthermore, lambs fed uninfected bovine colostrum readily seroconverted when mixed with ovine-colostrum lambs indicating that horizontal MVV transmission between lambs was efficient. MVV-infection was further investigated in the same samples using two PCR tests targeting sequences in the long-terminal repeats (LTR) and POL MVV genes. PCR-tests confirmed previous serological findings. However, the LTR-PCR was more sensitive and allowed detecting infection earlier than the other tests, including 5-8% of new-born lambs from seropositive dams, providing more evidence that prenatal MVV-infection may be more important than considered. The degree of agreement between PCR and antibody tests in individual samples was low up to 6 months of age and moderate at 10 months-old. Nine percent of lambs were always PCR-negative but seroconverted and 19% of lambs were PCR-positive at least once and did not seroconvert. However, seroconversion was associated with increasing number of times lambs were PCR-positive and ovine colostrum-fed lambs were more frequently PCR-positive than other lambs. The significance of these findings in terms of MVV-infection, epidemiology and control is discussed.


Assuntos
Anticorpos Antivirais/sangue , Colostro/virologia , Transmissão Vertical de Doenças Infecciosas/veterinária , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Pneumonia Intersticial Progressiva dos Ovinos/transmissão , Vírus Visna-Maedi/genética , Vírus Visna-Maedi/isolamento & purificação , Envelhecimento , Animais , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Masculino , Razão de Chances , Pneumonia Intersticial Progressiva dos Ovinos/sangue , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Reação em Cadeia da Polimerase/veterinária , Ovinos
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