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1.
J Wildl Dis ; 53(1): 170-175, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27763827

RESUMO

The recent increase in the creation of transboundary protected areas and wildlife corridors between them lends importance to information on pathogen prevalence and transmission among wildlife species that will become connected. One such initiative is the Kavango Zambezi Transfrontier Conservation Area of which Botswana's Okavango Delta constitutes a major contribution for wildlife and ecosystems. Between 2008 and 2011, we collected serum samples from 14 lions ( Panthera leo ), four leopards ( Panthera pardus ), 19 spotted hyenas ( Crocuta crocuta ), and six cheetahs ( Acinonyx jubatus ) in the Okavango. Samples were tested for antibodies against canine distemper virus (CDV), feline panleukopenia virus, enteric coronavirus, feline calicivirus, feline herpesvirus (FHV-1), and feline immunodeficiency virus (FIV). Evidence of exposure to all of these pathogens was found, to varying degrees, in at least one of the species sampled. High antibody prevalence (>90%) was only found to FHV-1 and FIV in lions. Only hyenas (26%, 5/19) were positive for CDV antibody. Except for one case, all individuals displayed physical conditions consistent with normal health for ≥12 mo following sampling. Our results emphasize the need for a comprehensive, multispecies approach to disease monitoring and the development of coordinated management strategies for subpopulations likely to be connected in transboundary initiatives.


Assuntos
Anticorpos Antivirais/análise , Hyaenidae/virologia , Leões/virologia , Animais , Botsuana , Vírus da Cinomose Canina , Lentivirus Felinos , Simpatria
2.
Mol Ther ; 22(1): 59-68, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23982166

RESUMO

Lentiviral vectors are widely used in basic research and clinical applications for gene transfer and long-term expression; however, safety issues have not yet been completely resolved. In this study, we characterized hepatocarcinomas that developed in mice 1 year after in utero administration of a feline-derived lentiviral vector. Mapped viral integration sites differed among tumors and did not coincide with the regions of chromosomal aberrations. Furthermore, gene expression profiling revealed that no known cancer-associated genes were deregulated in the vicinity of viral integrations. Nevertheless, five of the six tumors exhibited highly significant upregulation of E2F target genes, of which a majority are associated with oncogenesis, DNA damage response, and chromosomal instability. We further show in vivo and in vitro that E2F activation occurs early on following transduction of both fetal mice and cultured human hepatocytes. On the basis of the similarities in E2F target gene expression patterns among tumors and the lack of evidence implicating insertional mutagenesis, we propose that transduction of fetal mice with a feline lentiviral vector induces E2F-mediated major cellular processes that drive hepatocytes toward uncontrolled proliferation culminating in tumorigenesis.


Assuntos
Fatores de Transcrição E2F/metabolismo , Feto , Vetores Genéticos/genética , Lentivirus Felinos/genética , Neoplasias Hepáticas/etiologia , Transdução Genética , Animais , Gatos , Transformação Celular Neoplásica/genética , Aberrações Cromossômicas , Dano ao DNA , Dosagem de Genes , Expressão Gênica , Regulação da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Mutagênese Insercional , Transcriptoma , Transgenes , Integração Viral
3.
J Vet Dent ; 30(2): 78-83, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24006716

RESUMO

Tooth resorption (TR) is one of the most common dental diseases in cats. Determination of risk factors has not yet been fully assessed and, to the best knowledge of the authors, this disease has never been studied in Portuguese cats. The objective of this case-control study was to determine type and distribution of TR lesions, evaluate risk factors, and establish relationships between variables in this disease. The study included data from 71 cats admitted for general anesthesia for various reasons. The cats were randomly selected. The inclusion criteria were availability of clinical history and owner permission. Cats with known oral disease were not excluded from the study. All cats received ultrasonic scaling and polishing of the teeth, a thorough oral examination, and full-mouth radiographs. A strong statistical relation was found between age and TR. The age group of 10 to 15-years showed an increased risk of 6.56 times for TR occurrence compared with the group 0 to 4-years of age. Presence of gingivitis in all index levels was related to an increased risk for TR. No relation was found between age or gingivitis index and lesion type. Mandibular third premolar and molar teeth were most commonly affected by TR, especially for type 1 lesions. Canine teeth were statistically more likely to have type 2 lesions. The trend for the canine teeth to be more affected with type 2 lesions needs further verification.


Assuntos
Doenças do Gato/etiologia , Reabsorção de Dente/veterinária , Fatores Etários , Animais , Dente Pré-Molar/patologia , Estudos de Casos e Controles , Gatos , Dente Canino/patologia , Profilaxia Dentária/veterinária , Raspagem Dentária/veterinária , Feminino , Hemorragia Gengival/complicações , Hemorragia Gengival/veterinária , Hipertrofia Gengival/complicações , Hipertrofia Gengival/veterinária , Gengivite/classificação , Gengivite/complicações , Gengivite/veterinária , Vírus da Imunodeficiência Felina/isolamento & purificação , Infecções por Lentivirus/complicações , Infecções por Lentivirus/veterinária , Lentivirus Felinos/isolamento & purificação , Masculino , Dente Molar/patologia , Portugal , Radiografia Dentária/veterinária , Medição de Risco , Reabsorção de Dente/etiologia
4.
Vet Immunol Immunopathol ; 143(3-4): 235-42, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21813188

RESUMO

Gene therapy approaches to the treatment of HIV infection have targeted both viral gene expression and the cellular factors that are essential for virus replication. However, significant concerns have been raised regarding the potential toxic effects of such therapies, the emergence of resistant viral variants and unforeseen biological consequences such as enhanced susceptibility to unrelated pathogens. Novel restriction factors formed by the fusion of the tripartite motif protein (TRIM5) and cyclophilin A (CypA), or "TRIMCyps", offer an effective antiviral defence strategy with a very low potential for toxicity. In order to investigate the potential therapeutic utility of TRIMCyps in gene therapy for AIDS, a synthetic fusion protein between feline TRIM5 and feline CypA was generated and transduced into cells susceptible to infection with feline immunodeficiency virus (FIV). The synthetic feline TRIMCyp was highly efficient at preventing infection with both HIV and FIV and the cells resisted productive infection with FIV from either the domestic cat or the puma. Feline TRIMCyp and FIV infection of the cat offers a unique opportunity to evaluate TRIMCyp-based approaches to genetic therapy for HIV infection and the treatment of AIDS.


Assuntos
Fusão Gênica Artificial , Proteínas de Transporte/genética , Ciclofilina A/genética , Lentivirus Felinos/genética , Proteínas Recombinantes de Fusão/metabolismo , Síndrome de Imunodeficiência Adquirida/terapia , Animais , Gatos/virologia , Terapia Genética , Humanos , Vírus da Imunodeficiência Felina/genética , Proteínas Recombinantes de Fusão/genética
5.
Vet Immunol Immunopathol ; 143(3-4): 215-20, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21715025

RESUMO

Retroviral restriction factor research is explaining long-standing lentiviral mysteries. Asking why a particular retrovirus cannot complete a critical part of its life cycle in cells of a particular species has been the starting point for numerous discoveries, including heretofore elusive functions of HIV-1 accessory genes. The potential for therapeutic application is substantial. Analyzing the feline immunodeficiency virus (FIV) life cycle has been instrumental and the source of some surprising observations in this field. FIV is restricted in cells of various primates by several restriction factors including APOBEC3 proteins and, uniquely, TRIM proteins from both Old and New World monkeys. In contrast, the feline genome does not encode functional TRIM5alpha or TRIMCyp proteins and HIV-1 is primarily blocked in feline cells by APOBEC3 proteins. These can be overcome by inserting FIV vif or even SIVmac vif into HIV-1. The domestic cat and its lentivirus are positioned to offer strategic research opportunities as the field moves forward.


Assuntos
Infecções por Lentivirus/veterinária , Lentivirus Felinos/imunologia , Lentivirus de Primatas/imunologia , Doenças dos Macacos/virologia , Animais , Gatos , Síndrome de Imunodeficiência Adquirida Felina/virologia , Vírus da Imunodeficiência Felina/imunologia , Infecções por Lentivirus/imunologia , Doenças dos Macacos/imunologia , Filogenia , Vírion/imunologia
6.
Vet Immunol Immunopathol ; 134(1-2): 14-24, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19896724

RESUMO

The interplay between viral and cellular factors determines the outcome of an initial contact between a given virus and its natural host or upon encounter of a novel host. Thus, the potential of inducing disease as well as crossing host species barriers are the consequences of the molecular interactions between the parasite and its susceptible, tolerant or resistant host. Cellular restriction factors, for instance APOBEC3 and TRIM5 proteins, targeting defined pathogens or groups of pathogens as well as viral genes counter-acting these cellular defense systems are of prime importance in this respect and may even represent novel targets for prevention and therapy of virus infections. Due to the importance of host-encoded antiviral restriction and viral counter-defense for pathogenicity and host tropism, the responsible molecular factors and mechanisms are currently under intense investigation. In this review we will introduce host restriction and retroviral counter-defense systems with a special emphasis on the cat and its naturally occurring exogenous retroviruses which is a valid model for human disease, a model that will contribute to increase our basic understanding and potential applications of these important aspects of host-virus interaction.


Assuntos
Proteínas de Transporte/fisiologia , Doenças do Gato/virologia , Citosina Desaminase/fisiologia , Infecções por Retroviridae/veterinária , Retroviridae/fisiologia , Animais , Gatos/virologia , Interações Hospedeiro-Patógeno/fisiologia , Vírus da Imunodeficiência Felina/fisiologia , Lentivirus Felinos/fisiologia , Vírus da Leucemia Felina/fisiologia , Infecções por Retroviridae/virologia , Integração Viral/fisiologia , Replicação Viral/fisiologia
7.
Vet Immunol Immunopathol ; 112(1-2): 67-77, 2006 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-16678276

RESUMO

Feline immunodeficiency virus (FIV) is a natural infection of domestic cats, which produces a disease with many similarities to human immunodeficiency virus (HIV) infection in man. The virus is an important cause of morbidity and mortality in pet cats worldwide. As such an effective vaccine is desirable both for its use in veterinary medicine and also as a model for the development of an HIV vaccine. A large number of candidate vaccines have been tested against feline immunodeficiency virus. These include inactivated virus and infected cell vaccines, DNA and viral vectored vaccines, subunit and peptide vaccines and vaccines using bacterial vectors. Ultimately, the development of inactivated virus and infected cell vaccines led to the release of the first licensed vaccine against FIV, in 2002. This review highlights some of the difficulties associated with the development of lentiviral vaccines and some of the lessons that have been learned in the FIV model that are of particular relevance to the development of HIV vaccines.


Assuntos
Doenças do Gato/prevenção & controle , Infecções por Lentivirus/veterinária , Lentivirus Felinos/imunologia , Vacinas Virais/isolamento & purificação , Vacinas contra a AIDS/isolamento & purificação , Animais , Doenças do Gato/imunologia , Gatos , Síndrome de Imunodeficiência Adquirida Felina/imunologia , Síndrome de Imunodeficiência Adquirida Felina/prevenção & controle , Variação Genética , Humanos , Vírus da Imunodeficiência Felina/genética , Vírus da Imunodeficiência Felina/imunologia , Infecções por Lentivirus/imunologia , Infecções por Lentivirus/prevenção & controle , Vacinação/efeitos adversos , Vacinação/veterinária , Vacinas de DNA/isolamento & purificação , Vacinas de Produtos Inativados/isolamento & purificação
8.
Virology ; 342(1): 60-76, 2005 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-16120451

RESUMO

Feline immunodeficiency virus (FIV) causes fatal disease in domestic cats via T cell depletion-mediated immunodeficiency. Pumas and lions are hosts for apparently apathogenic lentiviruses (PLV, LLV) distinct from FIV. We compared receptor use among these viruses by: (1) evaluating target cell susceptibility; (2) measuring viral replication following exposure to specific and non-specific receptor antagonists; and (3) comparing Env sequence and structural motifs. Most isolates of LLV and PLV productively infected domestic feline T cells, but differed from domestic cat FIV by infecting cells independent of CXCR4, demonstrating equivalent or enhanced replication following heparin exposure, and demonstrating substantial divergence in amino acid sequence and secondary structure in Env receptor binding domains. PLV infection was, however, inhibited by CD134/OX40 antibody. Thus, although PLV and LLV infection interfere with FIV superinfection, we conclude that LLV and PLV utilize novel, more promiscuous mechanisms for cell entry than FIV, underlying divergent tropism and biological properties of these viruses.


Assuntos
Lentivirus Felinos/patogenicidade , Sequência de Aminoácidos , Animais , Sequência de Bases , Gatos , Linhagem Celular , DNA Viral/genética , Glicosilação , Vírus da Imunodeficiência Felina/genética , Vírus da Imunodeficiência Felina/imunologia , Vírus da Imunodeficiência Felina/patogenicidade , Vírus da Imunodeficiência Felina/fisiologia , Lentivirus Felinos/genética , Lentivirus Felinos/imunologia , Lentivirus Felinos/fisiologia , Leões , Dados de Sequência Molecular , Puma , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/fisiologia , Receptores OX40 , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Receptores Virais/antagonistas & inibidores , Receptores Virais/fisiologia , Homologia de Sequência de Aminoácidos , Linfócitos T/imunologia , Linfócitos T/virologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/fisiologia , Virulência , Replicação Viral
9.
AIDS ; 18(9): 1241-50, 2004 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-15362656

RESUMO

OBJECTIVE: As distal sensory polyneuropathy (DSP) is a major neurological complication of HIV-1 infection, we investigated the extent of peripheral nervous system disease in animals infected with the lentivirus, feline immunodeficiency virus (FIV), because it causes neurological disease and immunosuppression in cats similar to HIV-1 in humans. METHODS: After infection with a neurovirulent FIV molecular clone, neurobehavioral testing, nerve morphology, viral detection and load measurements were performed. RESULTS: Neurobehavioral studies showed delayed withdrawal in response to a noxious stimulus among FIV-infected animals compared with sham-infected controls (P < 0.05). Dorsal root ganglia and sciatic nerves from FIV-infected ammals showed activated macrophages that were increased in number and size compared with controls. In addition, TNF-alpha messenger RNA was detectable in most nerves and spinal cords from the FIV-infected group, but was infrequently detected in controls. Viral RNA copy numbers in plasma and sciatic nerves were detectable in all FIV-infected animals at high levels. Studies of sural nerves identified myelinated fiber atrophy in 12-week FIV-infected animals compared with age-matched control animals, which was accompanied by reduced myelin sheath thickness (P < 0.05). The footpads of FIV-infected animals displayed reduced intraepidermal fiber density compared with control animals (P < 0.01). CONCLUSION: FIV infection results in the rapid onset of peripheral neuropathy, defined by axonal injury and macrophage activation, together with abundant virus within the nerve, indicating that it may serve as a model of HIV-related DSP.


Assuntos
Doenças do Gato/imunologia , Infecções por Lentivirus/imunologia , Lentivirus Felinos , Doenças do Sistema Nervoso Periférico/virologia , Animais , Axônios/patologia , Comportamento Animal , Doenças do Gato/patologia , Gatos , Feminino , Gânglios Espinais/imunologia , Infecções por Lentivirus/patologia , Ativação de Macrófagos , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Amielínicas/patologia , Doenças do Sistema Nervoso Periférico/patologia , Nervo Isquiático/imunologia , Nervo Sural/patologia
10.
Biochem Biophys Res Commun ; 320(3): 998-1006, 2004 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-15240147

RESUMO

Liver-directed gene therapy has the potential for treatment of numerous inherited diseases affecting metabolic functions. The aim of this study was to evaluate gene expression in hepatocytes using feline immunodeficiency virus-based lentiviral vectors, which may be potentially safer than those based on human immunodeficiency virus. In vitro studies revealed that gene expression was stable for up to 24 days post-transduction and integration into the host cell genome was suggested by Alu PCR and Southern blot analyses. Systemic in vivo administration of viral particles by the hydrodynamics method resulted in high levels of gene expression exclusively in the liver for over 7 months whereas injection of plasmid DNA by the same method led to transient expression levels. Our studies suggest that feline immunodeficiency-based lentiviral vectors specifically transduce liver cells and may be used as a novel vehicle of gene delivery for treatment of metabolic disease.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica/genética , Vírus da Imunodeficiência Felina/genética , Transfecção/métodos , Animais , Gatos , Linhagem Celular Tumoral , Síndrome de Imunodeficiência Adquirida Felina/genética , Síndrome de Imunodeficiência Adquirida Felina/virologia , Terapia Genética/métodos , Vetores Genéticos/genética , Humanos , Lentivirus Felinos/genética , Primatas , Transgenes/genética
11.
J Virol ; 75(11): 5129-40, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11333894

RESUMO

Development of safe and effective gene transfer systems is critical to the success of gene therapy protocols for human diseases. Currently, several primate lentivirus-based gene transfer systems, such as those based on human and simian immunodeficiency viruses (HIV/SIV), are being tested; however, their use in humans raises safety concerns, such as the generation of replication-competent viruses through recombination with related endogenous retroviruses or retrovirus-like elements. Due to the greater phylogenetic distance from primate lentiviruses, feline immunodeficiency virus (FIV) is becoming the lentivirus of choice for human gene transfer systems. However, the safety of FIV-based vector systems has not been tested experimentally. Since lentiviruses such as HIV-1 and SIV have been shown to cross-package their RNA genomes, we tested the ability of FIV RNA to get cross-packaged into primate lentivirus particles such as HIV-1 and SIV, as well as a nonlentiviral retrovirus such as Mason-Pfizer monkey virus (MPMV), and vice versa. Our results reveal that FIV RNA can be cross-packaged by primate lentivirus particles such as HIV-1 and SIV and vice versa; however, a nonlentivirus particle such as MPMV is unable to package FIV RNA. Interestingly, FIV particles can package MPMV RNA but cannot propagate the vector RNA further for other steps of the retrovirus life cycle. These findings reveal that diverse retroviruses are functionally more similar than originally thought and suggest that upon coinfection of the same host, cross- or copackaging may allow distinct retroviruses to generate chimeric variants with unknown pathogenic potential.


Assuntos
Vetores Genéticos , Lentivirus Felinos/genética , Lentivirus de Primatas/genética , RNA Viral , Animais , Células COS , Capsídeo/metabolismo , Técnicas de Transferência de Genes , HIV-1/genética , HIV-1/crescimento & desenvolvimento , Humanos , Lentivirus Felinos/crescimento & desenvolvimento , Lentivirus de Primatas/crescimento & desenvolvimento , Vírus dos Macacos de Mason-Pfizer/genética , Vírus dos Macacos de Mason-Pfizer/crescimento & desenvolvimento , Homologia de Sequência , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Especificidade da Espécie , Transformação Genética
12.
Semin Vet Med Surg (Small Anim) ; 10(4): 251-5, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8820600

RESUMO

Human immunodeficiency virus and feline immunodeficiency virus are both lentiviruses that cause immunosuppressive disease. Similarities between these diseases have promoted the study of feline immunodeficiency virus as a model for human immunodeficiency virus. Not only have lentiviruses been found in domestic cats but they have been found in nondomestic felids as well. Florida panthers, African lions, and other nondomestic felids have been found to have antibodies directed against lentiviruses and each nondomestic cat has antibodies to a virus that is specific for that species. The phylogenetic relationships of these lentiviruses have been studied and mapped using nucleic acid sequencing technology. Phylogenetic mapping has been an important step for future development of vaccines and antiviral therapy.


Assuntos
Carnívoros , Infecções por Lentivirus/veterinária , Lentivirus Felinos , Animais , Anticorpos Antivirais/sangue , Gatos , Feminino , Infecções por Lentivirus/epidemiologia , Infecções por Lentivirus/imunologia , Infecções por Lentivirus/virologia , Lentivirus Felinos/genética , Lentivirus Felinos/imunologia , Masculino , Filogenia
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