RESUMEN
Polyomavirus infection often results in persistence of the viral genome with little or no virion production. However, infection of certain cell types can result in high viral gene transcription and either cytolysis or neoplastic transformation. While infection by polyomavirus is common in humans and many animals, major questions regarding viral persistence of most polyomaviruses remain unanswered. Specifically, identification of target cells for viral infection and the mechanisms polyomaviruses employ to maintain viral genomes within cells are important not only in ascribing causality to polyomaviruses in disease, but in understanding specific mechanisms by which they cause disease. Here, we characterize the cell of origin in raccoon polyomavirus (RacPyV)-associated neuroglial brain tumours as a neural stem cell. Moreover, we identify an association between the viral genome and the host cell bromodomain protein, BRD4, which is involved in numerous cellular functions, including cell cycle progression, differentiation of stem cells, tethering of persistent DNA viruses, and regulation of viral and host-cell gene transcription. We demonstrate that inhibition of BRD4 by the small molecule inhibitors (+)-JQ1 and IBET-151 (GSK1210151A) results in reduced RacPyV genome within cells in vitro, as well as significant reduction of viral gene transcripts LT and VP1, highlighting its importance in both maintenance of the viral genome and in driving oncogenic transformation by RacPyV. This work implicates BRD4 as a central protein involved in RacPyV neuroglial tumour cell proliferation and in the maintenance of a stem cell state.
Asunto(s)
Neuroglía/virología , Infecciones por Polyomavirus/veterinaria , Poliomavirus/genética , Mapaches/virología , Células Madre/virología , Factores de Transcripción/metabolismo , Infecciones Tumorales por Virus/veterinaria , Proteínas Virales/genética , Animales , Proliferación Celular , Transformación Celular Neoplásica , Genoma Viral , Neuroglía/metabolismo , Poliomavirus/metabolismo , Infecciones por Polyomavirus/metabolismo , Infecciones por Polyomavirus/fisiopatología , Infecciones por Polyomavirus/virología , Células Madre/metabolismo , Factores de Transcripción/genética , Transcripción Genética , Infecciones Tumorales por Virus/metabolismo , Infecciones Tumorales por Virus/fisiopatología , Infecciones Tumorales por Virus/virología , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: Infectious diarrhea can be caused by bacteria, viruses, or protozoan organisms, or a combination of these. The identification of co-infections in dogs is important to determine the prognosis and to plan strategies for their treatment and prophylaxis. Although many pathogens have been individually detected with real-time polymerase chain reaction (PCR), a comprehensive panel of agents that cause diarrhea in privately owned dogs has not yet been established. The objective of this study was to use a real-time PCR diarrhea panel to survey the frequencies of pathogens and co-infections in owned dogs attended in a veterinary hospital with and without diarrhea, as well the frequency in different countries. Feces samples were tested for canine distemper virus, canine coronavirus, canine parvovirus type 2 (CPV-2), Clostridium perfringens alpha toxin (CPA), Cryptosporidium spp., Giardia spp., and Salmonella spp. using molecular techniques. RESULTS: In total, 104 diarrheic and 43 control dogs that were presented consecutively at a major private veterinary hospital were included in the study. Overall, 71/104 (68.3%) dogs with diarrhea were positive for at least one pathogen: a single infection in 39/71 dogs (54.9%) and co-infections in 32/71 dogs (45.1%), including 21/32 dogs (65.6%) with dual, 5/32 (15.6%) with triple, and 6/32 (18.8%) with quadruple infections. In the control group, 13/43 (30.2%) dogs were positive, all with single infections only. The most prevalent pathogens in the diarrheic dogs were CPA (40/104 dogs, 38.5%), CPV-2 (36/104 dogs, 34.6%), and Giardia spp. (14/104 dogs, 13.5%). CPV-2 was the most prevalent pathogen in the dual co-infections, associated with CPA, Cryptosporidium spp., or Giardia spp. No statistical difference (P = 0.8374) was observed in the duration of diarrhea or the number of deaths (P = 0.5722) in the presence or absence of single or co-infections. CONCLUSIONS: Diarrheic dogs showed a higher prevalence of pathogen infections than the controls. Whereas the healthy dogs had only single infections, about half the diarrheic dogs had co-infections. Therefore, multiple pathogens should be investigated in dogs presenting with diarrhea. The effects of multiple pathogens on the disease outcomes remain unclear because the rate of death and the duration of diarrhea did not seem to be affected by these factors.
Asunto(s)
Infecciones Bacterianas/veterinaria , Coinfección/veterinaria , Diarrea/veterinaria , Enfermedades de los Perros/microbiología , Enfermedades Gastrointestinales/veterinaria , Enfermedades Parasitarias en Animales/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Envejecimiento , Animales , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/diagnóstico , Coinfección/microbiología , Coinfección/parasitología , Diarrea/microbiología , Diarrea/parasitología , Enfermedades de los Perros/etiología , Perros , Heces/microbiología , Heces/parasitología , Femenino , Enfermedades Gastrointestinales/etiología , Masculino , Enfermedades Parasitarias en Animales/parasitología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
BACKGROUND: Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC), associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV), associated with respiratory disease. FINDINGS: In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3). The three major ORFs of CnBoV3 (NS1, NP1 and VP1) shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. CONCLUSIONS: We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal's complex disease remains to be determined.
Asunto(s)
Bocavirus/clasificación , Bocavirus/aislamiento & purificación , Enfermedades de los Perros/virología , Hígado/virología , Infecciones por Parvoviridae/veterinaria , Animales , Secuencia de Bases , Bocavirus/genética , Análisis por Conglomerados , ADN Viral/química , ADN Viral/genética , Perros , Secuenciación de Nucleótidos de Alto Rendimiento , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Infecciones por Parvoviridae/virología , Filogenia , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
Echinococcus multilocularis is a zoonotic tapeworm, whose metacestode larval stage is the etiological agent for alveolar echinococcosis in humans and is a parasite of emerging concern according to the World Health Organization which is difficult to diagnose and has a case mortality rate of >90% when left untreated. Echinococcus multilocularis requires two mammalian hosts to complete its lifecycle: wild and domestic canids as definitive hosts, and small mammals (mostly rodents) as intermediate ones. Because of their close relations with humans, domestic dogs have been indicated as a mean of infection to people. Human alveolar echinococcosis has historically been rare in North America, however, since 2013, at least seventeen diagnoses have been confirmed in Alberta, Canada. Because of this unprecedented series of cases, assessing the frequency of infections in dogs in Alberta is key to estimate risk for dog owners and animal health professionals. This study was carried out in Edmonton to determine the frequency of E. multilocularis infection in domestic dogs and potential risk factors. Fecal samples and corresponding behavior risk surveys were collected from 775 dogs in seven urban off-leash parks within Edmonton city limits during the summer of 2020. A quantitative PCR fecal test was used to diagnose E. multilocularis infection. We found a single case of E. multilocularis infection (1/775) and determined that the overall true prevalence was 0.2% (95% CrI: 0.0-0.7%) corrected for detection sensitivity and specificity. Overall, these findings confirm the presence of E. multilocularis infection in domestic dogs in Edmonton although further work is required to fully understand the risk factors that may contribute to infection and potential transmission to humans.
Asunto(s)
Enfermedades de los Perros , Equinococosis , Echinococcus multilocularis , Enfermedades de los Roedores , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/parasitología , Perros , Equinococosis/epidemiología , Equinococosis/parasitología , Equinococosis/veterinaria , Heces/parasitología , Humanos , RoedoresRESUMEN
Introduction: Diarrhea is the second most common cause of mortality in shelter kittens. Studies examining prevention strategies in this population are lacking. Probiotics are of particular interest but studies in cats are largely limited to healthy adults or those with induced disease. Only one study in domestic cats describes the use of host-derived bacteria as a probiotic. We previously identified Enterococcus hirae as a dominant species colonizing the small intestinal mucosa in healthy shelter kittens. Oral administration of a probiotic formulation of kitten-origin E. hirae (strain 1002-2) mitigated the increase in intestinal permeability and fecal water loss resulting from experimental enteropathogenic E. coli infection in purpose-bred kittens. Based on these findings, we hypothesized that administration of kitten-origin E. hirae to weaned fostered shelter kittens could provide a measurable preventative health benefit. Methods: We conducted a randomized, placebo-controlled, blinded clinical trial to determine the impact of a freeze-dried E. hirae probiotic on body weight gain, incidence of diarrhea, carriage of potential diarrheal pathogens, and composition of the intestinal microbiota in weaned fostered shelter kittens. Results: One-hundred thirty kittens completed the study. Fifty-eight kittens received the probiotic and 72 received the placebo. There were no significant differences in age, weight upon initiation of the study, number of days in the study, average daily gain in body weight, or weight at completion of the study. Kittens treated with E. hirae were 3.4 times less likely to develop diarrhea compared to kittens treated with placebo (odds ratio = 0.294, 95% CI 0.109-0.792, p = 0.022). A significant impact of E. hirae was not observed on the presence or abundance of 30 different bacterial, viral, protozoal, fungal, algal, and parasitic agents in feces examined by qPCR. With exception to a decrease in Megamonas, administration of the E. hirae probiotic did not alter the predominant bacterial phyla present in feces based on 16S rRNA gene amplicon sequencing. Discussion: Decreased incidence of diarrhea associated with preventative administration of E. hirae to foster kittens supports a rationale for use of E. hirae for disease prevention in this young population at high risk for intestinal disease though additional studies are warranted.
RESUMEN
Longitudinal studies of cats naturally infected with feline leukemia virus (FeLV) are important for understanding disease outcomes. Levels of p27 antigen and copy numbers of proviral DNA have been associated with FeLV-infection courses. The purpose of this prospective study was to establish cutoff values for p27 antigen concentration and proviral DNA load that distinguished high positive from low positive groups of cats and to evaluate an association with survival. At enrollment, 254 cats were tested by point-of-care and microtiter plate enzyme-linked immunosorbent assays (ELISAs) for p27 antigen and real-time polymerase chain reaction (PCR) for proviral DNA. The 127 positive cats were retested monthly for six months and monitored for survival over the four-year study. A receiver operating characteristic-based analysis of samples with concordant or discordant qualitative results for p27 antigen and proviral DNA was used to establish cutoff values, and when applied to test results at enrollment for classifying cats as high positive or low positive, a significant difference in survival was observed. High positive cats had a median survival of 1.37 years (95% CI 0.83-2.02) from time of enrollment, while most low positive cats were still alive (93.1% survival). Quantitative results for p27 antigen concentration and proviral DNA load were highly correlated with survival times in FeLV-infected cats.
Asunto(s)
Antígenos Virales/metabolismo , Virus de la Leucemia Felina/fisiología , Leucemia Felina/virología , Infecciones por Retroviridae/veterinaria , Animales , Antígenos Virales/análisis , Antígenos Virales/genética , Gatos , ADN Viral/genética , ADN Viral/metabolismo , Femenino , Dosificación de Gen , Virus de la Leucemia Felina/genética , Leucemia Felina/mortalidad , Estudios Prospectivos , Provirus/genética , Provirus/fisiología , Infecciones por Retroviridae/mortalidad , Infecciones por Retroviridae/virología , Carga ViralRESUMEN
An unexplained outbreak of feline diarrhea and vomiting, negative for common enteric viral and bacterial pathogens, was subjected to viral metagenomics and PCR. We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and identified three different feline bocaviruses shed by 9/17 cats. Also detected were nucleic acids from attenuated vaccine viruses, members of the normal feline virome, viruses found in only one or two cases, and viruses likely derived from ingested food products. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease.
Asunto(s)
Bocavirus/aislamiento & purificación , Enfermedades de los Gatos/virología , Diarrea/veterinaria , Parvovirinae/aislamiento & purificación , Viroma , Vómitos/veterinaria , Animales , Bocavirus/clasificación , Bocavirus/genética , Bocavirus/fisiología , Colombia Británica/epidemiología , Enfermedades de los Gatos/epidemiología , Gatos , Diarrea/epidemiología , Diarrea/virología , Brotes de Enfermedades , Heces/virología , Femenino , Genoma Viral , Masculino , Parvovirinae/clasificación , Parvovirinae/genética , Parvovirinae/fisiología , Filogenia , Vómitos/epidemiología , Vómitos/virologíaRESUMEN
Feline leukemia virus (FeLV) is an oncogenic retrovirus of cats. While higher viral RNA and proviral DNA loads have been correlated with progressive infections and disease, a similar correlation has been suggested for p27 antigen concentrations. This analytical study compared the results of a quantitative ELISA for p27 antigen with quantitative real-time PCR results for FeLV proviral DNA in patient samples. A significant positive correlation between copies of proviral DNA and the concentration of p27 antigen was identified (râ¯=â¯0.761, Pâ¯<â¯0.0001). Samples with high proviral DNA loads, at least 1â¯×â¯106 copies/mL of whole blood, typically had p27 antigen concentrations greater than 30â¯ng/mL in plasma. Samples with proviral DNA loads below this level all had concentrations of p27 antigen in plasma that were less than 10â¯ng/mL. Given this correlation, it is hypothesized that the concentration of p27 antigen at a given point in time may help to indicate the likelihood of a progressive or regressive infection similar to what has been demonstrated for proviral DNA loads.
Asunto(s)
ADN Viral/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Virus de la Leucemia Felina/genética , Virus de la Leucemia Felina/inmunología , Antígeno Nuclear de Célula en Proliferación/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Animales , Gatos , ADN Viral/genética , Antígeno Nuclear de Célula en Proliferación/inmunología , Provirus/genética , Infecciones por Retroviridae/diagnóstico , Infecciones por Retroviridae/veterinaria , Infecciones por Retroviridae/virología , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/veterinaria , Infecciones Tumorales por Virus/virología , Carga Viral/métodosRESUMEN
Feces from dogs in an unexplained outbreak of diarrhea were analyzed by viral metagenomics revealing the genome of a novel parvovirus. The parvovirus was named cachavirus and was classified within the proposed Chapparvovirus genus. Using PCR, cachavirus DNA was detected in two of nine tested dogs from that outbreak. In order to begin to elucidate the clinical impact of this virus, 2,053 canine fecal samples were screened using real-time PCR. Stool samples from 203 healthy dogs were positive for cachavirus DNA at a rate of 1.47%, while 802 diarrhea samples collected in 2017 and 964 samples collected in 2018 were positive at rates of 4.0% and 4.66% frequencies, respectively (healthy versus 2017-2018 combined diarrhea p-value of 0.05). None of 83 bloody diarrhea samples tested positive. Viral loads were generally low with average real-time PCR Ct values of 36 in all three positive groups. The species tropism and pathogenicity of cachavirus, the first chapparvovirus reported in feces of a placental carnivore, remains to be fully determined.
Asunto(s)
ADN Viral , Diarrea/veterinaria , Enfermedades de los Perros/virología , Infecciones por Parvoviridae/veterinaria , Parvovirus/genética , Animales , Biología Computacional/métodos , Perros , Genoma Viral , Metagenómica/métodosRESUMEN
A viral metagenomic analysis of feces from an unexplained outbreak of feline diarrhea revealed the presence of Lyon-IARC polyomavirus (LIPyV) DNA. LIPyV, whose genome was originally sequenced from swabs of human skin, was fecally shed by three out of five diarrheic cats.
RESUMEN
We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses.
RESUMEN
Hemoplasmas were detected in two apparently healthy captive South American coatis (Nasua nasua) from southern Brazil during an investigation for vector-borne pathogens. Blood was subjected to packed cell volume (PCV) determination, a commercial real-time PCR panel for the detection of Anaplasma spp., Babesia spp., Bartonella spp., Hepatozoon spp., Leishmania spp., Mycoplasma haemofelis, 'Candidatus Mycoplasma turicensis', 'Candidatus Mycoplasma haemominutum', Neorickettsia risticii, Rickettsia rickettsii and Leptospira spp., and a pan-hemoplasma conventional PCR assay. PCV was normal, but both coatis tested positive for hemoplasmas and negative for all the remaining pathogens tested. Using different techniques for microscopy (light, confocal or SEM), structures compatible with hemoplasmas were identified. Sequencing of the 16S rRNA gene identified an organism resembling Mycoplasma haemofelis and another hemotropic Mycoplasma sp., with a sequence identity of 96.8% to a Mycoplasma sp. previously detected in capybaras.
Asunto(s)
Infecciones por Mycoplasma/veterinaria , Mycoplasma/aislamiento & purificación , Procyonidae/microbiología , Animales , Animales Domésticos , Animales Salvajes/microbiología , Brasil/epidemiología , ADN Bacteriano/genética , Femenino , Masculino , Microscopía , Microscopía Confocal , Microscopía Electrónica de Rastreo/métodos , Mycoplasma/genética , Mycoplasma/ultraestructura , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/microbiología , Infecciones por Mycoplasma/transmisión , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
Hemoplasmas, the erythrocyte-associated mycoplasmas, have been detected in several primates, causing mostly subclinical infection. This study aimed to determine the prevalence of hemoplasma infection in captive and free-ranging monkeys from southern Brazil, as well as factors and hematological abnormalities associated with infection. Blood samples from 40 non-human primates (NHP) were tested for hemoplasmas and coinfections. An overall of 10/40 (25.0%) NHP tested positive for hemoplasmas using PCR-based assays, including 9/14 (64.3%) black howler monkeys (Alouatta caraya) and 1/24 (4.2%) black-horned capuchin (Sapajus nigritus). Infection was not statistically associated with anemia, but wild-born monkeys and male black howler monkeys were more likely to be positive when compared with captive-born animals and female black howler monkeys, respectively. The sequences from the black howler monkey hemoplasma were similar (94% identity) to the squirrel monkey hemoplasma ("Candidatus Mycoplasma kahanei") and were phylogenetically located in a different cluster when compared to the human hemoplasma ("Candidatus Mycoplasma haemohominis").
Asunto(s)
Alouatta/microbiología , Callithrix/microbiología , Cebinae/microbiología , Enfermedades de los Monos/epidemiología , Infecciones por Mycoplasma/veterinaria , Mycoplasma/aislamiento & purificación , Animales , Animales Salvajes/microbiología , Brasil/epidemiología , Coinfección/sangre , Coinfección/microbiología , Eritrocitos/microbiología , Enfermedades de los Monos/sangre , Enfermedades de los Monos/microbiología , Mycoplasma/genética , Infecciones por Mycoplasma/sangre , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/microbiología , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
INTRODUCTION: Cart horses are a re-emerging population employed to carry recyclable material in cities. METHODS: Sixty-two horses were sampled in an endemic area of human leptospirosis. The microscopic agglutination test (MAT) and real-time polymerase chain reaction (qPCR) were performed. RESULTS: A seropositivity of 75.8% with serovar Icterohaemorrhagiae in 80.8% of the horses was observed. Blood and urine were qPCR negative. MAT showed positive correlations with rainfall (p = 0.02) and flooding (p = 0.03). CONCLUSIONS: Although horses may be constantly exposed to Leptospira spp. in the environment mostly because of rainfall and flooding, no leptospiremia or leptospiruria were observed in this study.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Enfermedades de los Caballos/epidemiología , Leptospira , Leptospirosis/veterinaria , Pruebas de Aglutinación/veterinaria , Animales , Brasil/epidemiología , Enfermedades de los Caballos/diagnóstico , Caballos , Humanos , Leptospira/genética , Leptospira/inmunología , Leptospirosis/diagnóstico , Leptospirosis/epidemiología , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Estudios Seroepidemiológicos , Población UrbanaRESUMEN
A 9-year-old female spayed Domestic Medium Hair cat presented to the referring veterinarian with a 2-week history of sneezing, which progressed to swelling over the nasal planum. The cat had been under veterinary care for inflammatory bowel disease and had been treated with 1.25 mg/kg prednisolone once a day for approximately 1 year. On physical examination, an approximately 2-3 mm diameter, round polypoid pink soft-tissue mass was protruding slightly from the right nostril. Through histologic examination of representative sections from the mass, there was a severe diffuse infiltrate of epithelioid macrophages and neutrophils that surrounded frequent 15-20 µm yeast organisms. A Grocott methenamine silver stain revealed the presence of pseudohyphae in addition to the previously noted yeast forms. Real-time polymerase chain reaction (PCR) for Cryptococcus neoformans, Ajellomyces dermatitidis (syn. Blastomyces dermatitidis), Coccidioides immitis, Ajellomyces capsulatus (syn. Histoplasma capsulatum), Malassezia spp., and Candida spp. was performed on the paraffin-embedded sample. The PCR for Candida spp. was positive; the product was then sequenced and was determined to be consistent with Candida parapsilosis. Following the PCR diagnosis and prior to treatment of the infection, C. parapsilosis was cultured from a nasal swab. The infection in the cat in the current report was considered opportunistic and secondary to immunosuppression, following treatment for the inflammatory bowel disease.
Asunto(s)
Candida/aislamiento & purificación , Candidiasis/veterinaria , Enfermedades de los Gatos/microbiología , Granuloma/veterinaria , Rinitis/veterinaria , Animales , Candida/genética , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , ADN de Hongos/genética , Femenino , Granuloma/tratamiento farmacológico , Granuloma/microbiología , Histocitoquímica/veterinaria , Huésped Inmunocomprometido , Itraconazol/uso terapéutico , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Rinitis/tratamiento farmacológico , Rinitis/microbiologíaRESUMEN
Hemotropic mycoplasmas are bacteria that infect erythrocytes and cause subclinical infections to life-threatening disease. We describe hemotropic mycoplasma infection in a free-ranging black howler monkey (Alouatta caraya). This is the first molecular detection of a hemotropic mycoplasma in a nonhuman primate from Brazil.
Asunto(s)
Alouatta , Enfermedades de los Monos/epidemiología , Infecciones por Mycoplasma/veterinaria , Animales , Animales Salvajes/microbiología , Brasil/epidemiología , Femenino , Enfermedades de los Monos/diagnóstico , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/epidemiologíaAsunto(s)
Enfermedades de los Gatos/diagnóstico , Dermatitis/veterinaria , Infecciones por Herpesviridae/veterinaria , Enfermedades Nasales/veterinaria , Enfermedades Respiratorias/veterinaria , 2-Aminopurina/análogos & derivados , 2-Aminopurina/uso terapéutico , Animales , Animales Salvajes , Antivirales/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Dermatitis/complicaciones , Dermatitis/diagnóstico , Dermatitis/patología , Diagnóstico Diferencial , Famciclovir , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/patología , Masculino , Enfermedades Nasales/complicaciones , Enfermedades Nasales/diagnóstico , Enfermedades Nasales/patología , Enfermedades Respiratorias/complicaciones , Enfermedades Respiratorias/diagnósticoRESUMEN
BACKGROUND: Murine cytomegalovirus (MCMV) is an etiologic agent of acute and chronic myocarditis in BALB/c mice. Immunologic host responses appear to play a key role in pathogenesis but have been incompletely defined. METHODS: BALB/c mice were infected with a sublethal dose of MCMV. Cytokine transcription and viral load (measured by quantitative real-time polymerase chain reaction) and histopathological analyses were performed at specified time points. RESULTS: Increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and interferon (IFN)-gamma, as well as IL-10 mRNA transcripts, were detected in the hearts of infected mice starting at Day 1 post-infection (p.i.), with peak levels occurring at Day 8 p.i. (7-fold, 14-fold, 41-fold, and 16-fold higher than background, respectively). Peak cytokine transcription significantly correlated with a 10-fold increase in viral load (P<.001) at Day 8 p.i. Myocarditis-related pathological changes, measured by infiltration foci, were greatest at Day 8 p.i., corresponding with peak cytokine transcription and significantly correlated with IFN-gamma levels (P<.0001). Infiltration foci were predominantly composed of CD3(+) T cells. Cardiac calcification was observed in most infected mice predominantly over the right ventricle. Histological analysis of heart sections from mice infected with recombinant enhanced green fluorescence protein-MCMV revealed a localized and sporadic pattern of virus throughout all heart layers. CONCLUSIONS: MCMV-induced myocarditis in BALB/c mice is characterized by in vivo production of proinflammatory cytokines in a pattern correlating with MCMV viral load. The infection pattern and inflammatory response is highly localized, sporadic, and involves endocardium, epicardium, as well as the myocardium, with greatest amounts of virus detected in areas of pathologic calcification.