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1.
Vet Anim Sci ; 20: 100293, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37284505

RESUMO

A 5-year-old female Beagle Dog was euthanized following ten days of inappetence, lethargy, and pain in the left cervical region that was not responsive to steroids or antibiotics. At necropsy, there were multiple soft dark red to tan nodules throughout all lung lobes, abundant purulent subdural exudate over the right temporal lobe of the brain, and minimally enlarged submandibular and tracheobronchial lymph nodes. Impression smear of the subdural pus and histologic section of the lung and meninges demonstrated small aggregates of rod-shaped to filamentous bacteria often surrounded by Splendori-Hoeppli material. Aerobic culture of the subdural exudate yielded pure growth of Actinomyces bowdenii. To our knowledge, this is the first report of central nervous disease or pneumonia associated with Actinomyces bowdenii.

2.
Nat Commun ; 13(1): 4610, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941149

RESUMO

ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirus-vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 has been shown to have 74% vaccine efficacy against symptomatic disease in clinical trials. However, variants of concern (VoCs) have been detected, with substitutions that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial, even though current real-world data is suggesting good efficacy following boosting with vaccines encoding the ancestral S protein. Using the Syrian hamster model, we evaluate the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. Minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 3- or 5- days post inoculation, in contrast to lungs of control animals. In Omicron-challenged hamsters, a single dose of AZD2816 or AZD1222 reduced virus shedding. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.


Assuntos
COVID-19 , Vacinas Virais , Animais , Anticorpos Antivirais , COVID-19/prevenção & controle , ChAdOx1 nCoV-19 , Cricetinae , Humanos , Mesocricetus , SARS-CoV-2
3.
Res Sq ; 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35194602

RESUMO

ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirusâ€"vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 was shown to have 74% vaccine efficacy (VE) against symptomatic disease in clinical trials and over 2.5 billion doses of vaccine have been released for worldwide use. However, SARS-CoV-2 continues to circulate and consequently, variants of concern (VoCs) have been detected, with substitutions in the S protein that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial over boosting with vaccines encoding the ancestral S protein, even though current real-world data is suggesting good efficacy against hospitalization and death following boosting with vaccines encoding the ancestral S protein. Using the Syrian hamster model, we evaluated the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. We then investigated the efficacy of a single dose of AZD2816 or AZD1222 against the Omicron VoC. As seen previously, minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 5 days post inoculation, in contrast to lungs of control animals. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.

4.
Viruses ; 13(12)2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34960775

RESUMO

Pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of COVID-19. Chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a Western Diet. For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome. We observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, and edema, delayed viral clearance and functional lung recovery, and prolonged viral shedding. This was accompanied by an altered, but not significantly different, systemic IL-10 and IL-6 profile, as well as a dysregulated serum lipid response dominated by polyunsaturated fatty acid-containing phosphatidylethanolamine, partially recapitulating cytokine and lipid responses associated with severe human COVID-19. Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19.


Assuntos
COVID-19 , Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Metabolismo dos Lipídeos , Índice de Gravidade de Doença , Animais , COVID-19/patologia , Cricetinae , Citocinas/sangue , Modelos Animais de Doenças , Edema , Fibrina , Hemorragia , Humanos , Interleucina-10 , Interleucina-6 , Lipidômica , Lipídeos/sangue , Fígado/patologia , Pulmão/patologia , Masculino , Mesocricetus , Obesidade , SARS-CoV-2 , Açúcares , Vasculite/patologia , Eliminação de Partículas Virais
5.
Emerg Infect Dis ; 22(6): 1031-7, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27070385

RESUMO

Middle East respiratory syndrome coronavirus is a recently emerged pathogen associated with severe human disease. Zoonotic spillover from camels appears to play a major role in transmission. Because of logistic difficulties in working with dromedaries in containment, a more manageable animal model would be desirable. We report shedding and transmission of this virus in experimentally infected alpacas (n = 3) or those infected by contact (n = 3). Infectious virus was detected in all infected animals and in 2 of 3 in-contact animals. All alpacas seroconverted and were rechallenged 70 days after the original infection. Experimentally infected animals were protected against reinfection, and those infected by contact were partially protected. Necropsy specimens from immunologically naive animals (n = 3) obtained on day 5 postinfection showed virus in the upper respiratory tract. These data demonstrate efficient virus replication and animal-to-animal transmission and indicate that alpacas might be useful surrogates for camels in laboratory studies.


Assuntos
Camelus/virologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Replicação Viral , Zoonoses , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Biópsia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Modelos Animais de Doenças , Humanos , Imunidade Humoral , Imuno-Histoquímica , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Avaliação de Sintomas , Eliminação de Partículas Virais
6.
Sci Rep ; 6: 21878, 2016 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-26899616

RESUMO

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.


Assuntos
Infecções por Coronavirus/veterinária , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Replicação Viral , Eliminação de Partículas Virais , Animais , Anticorpos Antivirais/sangue , Quirópteros/virologia , Chlorocebus aethiops , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Cricetinae , Dipeptidil Peptidase 4/metabolismo , Imunidade Inata , Pulmão/patologia , Pulmão/virologia , Receptores Virais/metabolismo , Células Vero , Carga Viral
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