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1.
World J Gastroenterol ; 26(19): 2323-2332, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32476796

RESUMO

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that causes coronavirus disease-2019 (COVID-19) is a global pandemic, manifested by an infectious pneumonia. Although patients primarily present with fever, cough and dyspnea, some patients also develop gastrointestinal (GI) and hepatic manifestations. The most common GI symptoms reported are diarrhea, nausea, vomiting, and abdominal discomfort. Liver chemistry abnormalities are common and include elevation of aspartate transferase, alanine transferase, and total bilirubin. Studies have shown that SARS-CoV-2 infects the GI tract via its viral receptor angiotensin converting enzyme II, which is expressed on enterocytes of the ileum and colon. Viral RNA has also been isolated from stool specimens of COVID-19 patients, which raised the concern for fecal-oral transmission in addition to droplet transmission. Although indirect evidence has suggested possible fecal-oral transmission of SARS-CoV-2, more effort is needed to establish the role of the fecal-oral transmission route. Further research will help elucidate the association between patients with underlying GI diseases, such as chronic liver disease and inflammatory bowel disease, and severity of COVID-19. In this review, we summarize the data on GI involvement to date, as well as the impact of COVID-19 on underlying GI diseases.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Gastroenteropatias/virologia , Hepatopatias/virologia , Pneumonia Viral/complicações , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Transmissão de Doença Infecciosa , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Trato Gastrointestinal/virologia , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Fígado/virologia , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia
2.
J Microbiol Immunol Infect ; 53(3): 473-480, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32276848

RESUMO

OBJECTIVE: To determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19). METHODS: From January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored. RESULTS: Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days. CONCLUSIONS: SARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Fezes/virologia , Trato Gastrointestinal/virologia , Pneumonia Viral/transmissão , Eliminação de Partículas Virais/fisiologia , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Pandemias , RNA Viral/isolamento & purificação , Sistema Respiratório/virologia
3.
Gut ; 69(6): 997-1001, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32241899

RESUMO

OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Trato Gastrointestinal , Pandemias , Pneumonia Viral , Adulto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Feminino , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia
4.
Gut ; 69(6): 1002-1009, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32213556

RESUMO

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus , Trato Gastrointestinal , Pandemias , Pneumonia Viral , Adulto , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Feminino , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Fatores de Risco
5.
Immunity ; 52(2): 241-255, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32075727

RESUMO

Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.


Assuntos
Asma/imunologia , Asma/microbiologia , Trato Gastrointestinal , Pulmão , Microbiota/imunologia , Animais , Asma/patologia , Asma/fisiopatologia , Disbiose/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/virologia , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/parasitologia , Pulmão/virologia , Sistema Respiratório/imunologia , Sistema Respiratório/microbiologia , Sistema Respiratório/parasitologia , Sistema Respiratório/virologia
7.
Transbound Emerg Dis ; 67(1): 199-205, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31483952

RESUMO

Porcine circovirus 3 (PCV-3) has been identified in pigs affected by different disease conditions, although its pathogenicity remains unclear. The objective of the present study was to assess the frequency of PCV-3 infection in serum samples from animals suffering from post-weaning respiratory or digestive disorders as well as in healthy animals. A total of 315 swine serum samples were analysed for PCV-3 DNA detection by conventional PCR; positive samples were further assayed with a quantitative PCR and partially sequenced. Sera were obtained from 4 week- to 4 month-old pigs clinically diagnosed with respiratory (n = 129) or digestive (n = 126) disorders. Serum samples of age-matched healthy animals (n = 60) served as negative control. Pigs with clinical respiratory signs had a wide variety of pulmonary lesions including suppurative bronchopneumonia, interstitial pneumonia, fibrinous-necrotizing pneumonia and/or pleuritis. Animals with enteric signs displayed histopathological findings like villus atrophy and fusion, catarrhal enteritis and/or catarrhal colitis. Overall, PCV-3 DNA was detected in 19 out of 315 analysed samples (6.0%). Among the diseased animals, PCV-3 was found in 6.2% (8 out of 129) and 5.6% (7 out of 126) of pigs with respiratory and digestive disorders, respectively. The frequency of PCV-3 PCR positive samples among healthy pigs was 6.7% (4 out of 60). No apparent association was observed between PCR positive cases and any type of histopathological lesion. The phylogenetic analysis of the partial genome sequences obtained showed high identity among viruses from the three groups of animals studied. In conclusion, PCV-3 was present in the serum of diseased and healthy pigs to similar percentages, suggesting that this virus does not seem to be causally associated with respiratory or enteric disorders.


Assuntos
Infecções por Circoviridae/veterinária , Circovirus/isolamento & purificação , Gastroenteropatias/veterinária , Transtornos Respiratórios/veterinária , Doenças dos Suínos/virologia , Animais , Infecções por Circoviridae/virologia , Circovirus/genética , DNA Viral/sangue , Gastroenteropatias/virologia , Trato Gastrointestinal/virologia , Pulmão/virologia , Filogenia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Transtornos Respiratórios/virologia , Suínos
8.
Vet Microbiol ; 239: 108462, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767100

RESUMO

In contrast to human influenza viruses that replicate in the respiratory tract and are airborne transmitted, avian viruses also replicate in gut epithelial cells and are transmitted via the fecal-oral route. On this route, the virus is exposed to destructive fluids of the digestive tract, which are acidic and contain the proteases pepsin (gizzard) or chymotrypsin and trypsin (intestine). Only the latter enzyme activates virus by cleaving hemagglutinin (HA) into HA1 and HA2 subunits. We mimicked the passage of viruses through the gastrointestinal tract by treating them with digestive fluids from chicken and determined titers and integrity of HA by western-blot. Gizzard fluid completely inactivated virions and degrades HA even at a high dilution, but only if the pH was kept acidic. If the fluid is diluted with neutral buffer (mimicking virus uptake with seawater) particles were more resistant. Virions containing an uncleaved HA were even activated suggesting that gastric juice contains a trypsin-like protease. Undiluted intestinal fluid inactivated particles and destroyed HA, but diluted fluid activated virions. A virus isolated from the duck´s intestine is more tolerant against intestinal fluid compared to fowl plague virus suggesting that the former is better adapted to grow in the intestine. We also demonstrate that influenza viruses replicate to high titers in a novel chicken epithelial gut cell line. While viruses with a monobasic HA cleavage site require addition of trypsin, these cells effectively process HA with a polybasic cleavage site, which could be blocked with an inhibitor of the cellular furin protease.


Assuntos
Trato Gastrointestinal/virologia , Hemaglutininas/metabolismo , Influenza Aviária/virologia , Animais , Galinhas , Células Epiteliais/citologia , Células Epiteliais/virologia , Suco Gástrico/química , Suco Gástrico/enzimologia , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Secreções Intestinais/química , Secreções Intestinais/enzimologia , Inativação de Vírus , Replicação Viral/fisiologia
9.
PLoS Negl Trop Dis ; 13(9): e0007716, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31557156

RESUMO

Japanese Encephalitis virus (JEV) is a zoonotic flavivirus that represents the most significant etiology of childhood viral neurological infections throughout the Asia. During the last 20 years, JEV genotype dominance has shifted from genotype III (GIII) to genotype I (GI). To date, the exact mechanism of this displacement is still not known. Culex (Cx.) mosquitoes are the most common species in China and play an essential role in maintaining JEV enzootic transmission cycle. In this study, we used Cx. pipiens mosquitoes from China as an in vivo mosquito model to explore if mosquitoes played a potential role in JEV genotype shift. We exposed female Cx. pipiens mosquitoes orally to either GI or GIII JEV strains. Midgut, whole mosquitoes, secondary organs, and salivary glands of JEV-infected mosquitoes were collected at 7 and 14 days of post infection (dpi) and subjected to measure the infection rate, replication kinetics, dissemination rate and transmission potential of the infected JEV strains in Cx. pipiens mosquitoes by 50% tissue culture infective dose assay. We found that Cx. pipiens mosquito was competent vector for both GI and GIII JEV infection, with similar infection rates and growth kinetics. After the establishment of infection, Cx. pipiens mosquitoes disseminated both JEV genotypes to secondary organs at similar rates of dissemination. A few GI-infected mosquito salivary glands (16.2%) were positive for GI virus, whereas GIII virus was undetectable in GIII-infected mosquito salivary glands at 7 dpi. However, 29.4% (5/17) and 36.3% (8/22) were positive for GI- and GIII-infected mosquito salivary glands at 14 dpi, respectively, showing an increase in JEV positive rate. No statistical difference in the transmission rate between GI- and GIII-infected mosquitoes was detected. Our experiment data demonstrated that GI and GIII viruses have similar infectivity in Cx. pipiens mosquitoes, suggesting that Cx. pipiens mosquitoes from China may not play a critical role in JEV genotype shift. Although the current data were obtained solely from Cx. pipiens mosquitoes, it is likely that the conclusion drawn could be extrapolated to the role of mosquitoes in JEV genotype shift.


Assuntos
Culex/virologia , Vírus da Encefalite Japonesa (Espécie)/genética , Animais , China , Vírus da Encefalite Japonesa (Espécie)/crescimento & desenvolvimento , Encefalite Japonesa/transmissão , Encefalite Japonesa/virologia , Feminino , Trato Gastrointestinal/virologia , Genótipo , Mosquitos Vetores/virologia , Glândulas Salivares/virologia
10.
Proc Natl Acad Sci U S A ; 116(38): 19136-19144, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31488709

RESUMO

Zika virus (ZIKV) is an arthropod-borne flavivirus predominantly transmitted by Aedes aegypti mosquitoes and poses a global human health threat. All flaviviruses, including those that exclusively replicate in mosquitoes, produce a highly abundant, noncoding subgenomic flavivirus RNA (sfRNA) in infected cells, which implies an important function of sfRNA during mosquito infection. Currently, the role of sfRNA in flavivirus transmission by mosquitoes is not well understood. Here, we demonstrate that an sfRNA-deficient ZIKV (ZIKVΔSF1) replicates similar to wild-type ZIKV in mosquito cell culture but is severely attenuated in transmission by Ae. aegypti after an infectious blood meal, with 5% saliva-positive mosquitoes for ZIKVΔSF1 vs. 31% for ZIKV. Furthermore, viral titers in the mosquito saliva were lower for ZIKVΔSF1 as compared to ZIKV. Comparison of mosquito infection via infectious blood meals and intrathoracic injections showed that sfRNA is important for ZIKV to overcome the mosquito midgut barrier and to promote virus accumulation in the saliva. Next-generation sequencing of infected mosquitoes showed that viral small-interfering RNAs were elevated upon ZIKVΔSF1 as compared to ZIKV infection. RNA-affinity purification followed by mass spectrometry analysis uncovered that sfRNA specifically interacts with a specific set of Ae. aegypti proteins that are normally associated with RNA turnover and protein translation. The DEAD/H-box helicase ME31B showed the highest affinity for sfRNA and displayed antiviral activity against ZIKV in Ae. aegypti cells. Based on these results, we present a mechanistic model in which sfRNA sequesters ME31B to promote flavivirus replication and virion production to facilitate transmission by mosquitoes.


Assuntos
Aedes/virologia , RNA Helicases DEAD-box/metabolismo , Proteínas de Insetos/metabolismo , Mosquitos Vetores/virologia , RNA Viral/genética , Infecção por Zika virus/transmissão , Zika virus/genética , Aedes/imunologia , Animais , Chlorocebus aethiops , RNA Helicases DEAD-box/genética , Trato Gastrointestinal/virologia , Genoma Viral , Proteínas de Insetos/genética , Glândulas Salivares/virologia , Replicação Viral , Zika virus/imunologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
11.
Am J Trop Med Hyg ; 101(3): 534-540, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31392942

RESUMO

Multiplex polymerase chain reaction (PCR) platforms have enhanced understanding of intestinal pathogens in low- and middle-income countries (LMICs). However, few such studies have been performed in Latin America, where poverty, poor sanitation, and undernutrition persist. Multiplex PCR (BioFire, Salt Lake City, UT) was used to identify viral, bacterial, and parasitic pathogens in stool collected on day 1 and 31 from children aged 6 to 35 months with acute, non-bloody diarrhea in two locations (rural and urban) in Guatemala. We analyzed correlation between pathogens and clinical, demographic, and socioeconomic variables; described patterns of pathogen acquisition, persistence, and clearance over the 30-day period; and calculated population attributable fractions (PAFs) for diarrheal causation for individual pathogens. We analyzed 316 subjects (144 urban; 172 rural) enrolled between March 2015 and January 2016. Rural subjects had significantly more malnutrition, animal exposure, and unimproved water/sanitation infrastructure. The majority of subjects had multiple pathogens/sample (4.8 rural and 2.7 urban). Few meaningful correlates were identified between individual pathogens and clinical, demographic, or environmental variables. Escherichia coli pathotypes, Shigella, Campylobacter, and Giardia had high rates of persistence between initial and 30-day follow-up. Statistically significant adjusted PAFs were identified for Campylobacter (14.9%, 95% CI: 3.2-23.1), norovirus (10.2%, 95% CI: 0.4-17.1), sapovirus (7.6%, 95% CI: 2.3-10.9), and adenovirus 40/41 (5.6%, 95% CI: 0.3-8.7). These observations further characterize the diversity and complexity of enteric pathogens in children in LMICs. Patterns of chronic symptomatic and asymptomatic infection among Latin American children are similar to those observed in other LMIC regions. Findings have direct implications for practitioners treating individuals with acute infectious diarrhea and should inform regional public health strategies.


Assuntos
Diarreia/diagnóstico , Reação em Cadeia da Polimerase Multiplex , População Rural , População Urbana , Doença Aguda , Animais , Bactérias/genética , Bactérias/patogenicidade , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/virologia , Diarreia/microbiologia , Diarreia/parasitologia , Diarreia/virologia , Feminino , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/virologia , Humanos , Lactente , Masculino , Parasitos/genética , Parasitos/patogenicidade , Vírus/genética , Vírus/patogenicidade
12.
PLoS Negl Trop Dis ; 13(8): e0007299, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31412040

RESUMO

BACKGROUND: To be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have to cross several barriers in the mosquito body, including the midgut infection and escape barriers. Yellow fever virus (YFV) belongs to the genus Flavivirus, which includes human viruses transmitted by Aedes mosquitoes, such as dengue and Zika viruses. The live-attenuated YFV-17D vaccine has been used safely and efficiently on a large scale since the end of World War II. Early studies have shown, using viral titration from salivary glands of infected mosquitoes, that YFV-17D can infect Aedes aegypti midgut, but does not disseminate to other tissues. METHODOLOGY/PRINCIPAL FINDINGS: Here, we re-visited this issue using a panel of techniques, such as RT-qPCR, Western blot, immunofluorescence and titration assays. We showed that YFV-17D replication was not efficient in Aedes aegypti midgut, as compared to the clinical isolate YFV-Dakar. Viruses that replicated in the midgut failed to disseminate to secondary organs. When injected into the thorax of mosquitoes, viruses succeeded in replicating into midgut-associated tissues, suggesting that, during natural infection, the block for YFV-17D replication occurs at the basal membrane of the midgut. CONCLUSIONS/SIGNIFICANCE: The two barriers associated with Ae. aegypti midgut prevent YFV-17D replication. Our study contributes to our basic understanding of vector-pathogen interactions and may also aid in the development of non-transmissible live virus vaccines.


Assuntos
Aedes/virologia , Trato Gastrointestinal/virologia , Replicação Viral/efeitos dos fármacos , Vacina contra Febre Amarela/farmacologia , Vírus da Febre Amarela/efeitos dos fármacos , Vírus da Febre Amarela/crescimento & desenvolvimento , Animais , Linhagem Celular , Trato Gastrointestinal/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Mosquitos Vetores , Glândulas Salivares , Vacinas Atenuadas , Carga Viral , Vírus da Febre Amarela/genética
13.
Curr HIV/AIDS Rep ; 16(3): 181-190, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31104270

RESUMO

PURPOSE OF REVIEW: The discovery of innate lymphoid cells (ILCs) over the past decade has reformed principles that were once thought to be exclusive to adaptive immunity. Here, we describe ILC nomenclature and function, and provide a survey of studies examining these cells in the context of HIV/SIV infections. Particular emphasis is placed on the ILC3 subset, important for proper functioning of the gastrointestinal tract barrier. RECENT FINDINGS: Studies in both humans and nonhuman primates have found ILCs to be rapidly and durably depleted in untreated HIV/SIV infections. Their depletion is most likely due to a number of bystander effects induced by viral replication. Given the number of associations observed between loss of ILCs and HIV-related GI damage, their impact on the GI tract is likely important. It may be informative to examine this subset in parallel with other immune cell types when assessing overall health of the GI tract in future studies.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Trato Gastrointestinal/virologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Homeostase , Humanos , Macaca mulatta/imunologia , Macaca mulatta/virologia , Camundongos , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia
14.
Vet Res ; 50(1): 35, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097029

RESUMO

Viral metagenomic analysis of the liver of a black headed python (Aspidites melanocephalus) euthanized for a proliferative spinal lesion of unknown etiology yielded the first characterized genome of a reptile-infecting circovirus (black-headed python circovirus or BhPyCV). BhPyCV-specific in situ hybridization (ISH) showed that viral nucleic acids were strongly expressed in the intestinal lining and mucosa and multifocally in the liver. To investigate the presence of this virus in other snakes and its possible pathogenicity, 17 snakes in the python family with spinal disease were screened with ISH yielding a second BhP positive in intestinal tissue, and a Boelen's python (Morelia boeleni) positive in the liver. BhPyCV specific PCR was used to screen available frozen tissues from 13 of these pythons, four additional deceased pythons with and without spinal disease, and fecal samples from 37 live snakes of multiple species with unknown disease status. PCR detected multiple positive tissues in both of the ISH positive BhP and in the feces of another two live BhP and two live annulated tree boas (Corallus annulatus). Preliminary analysis indicates this circovirus can infect BhPs where it was found in 4/5 BhPs tested (2/2 with spinal disease, 2/3 live with unknown status), Boelen's python (1/2 with spinal disease), and annulated tree boa (2/6 live with unknown status) but was not detected in other python species with the same spinal lesions. This circovirus' causal or contributory role in spinal disease remains speculative and not well supported by these initial data.


Assuntos
Boidae/virologia , Infecções por Circoviridae/veterinária , Circovirus , Trato Gastrointestinal/virologia , Fígado/virologia , Animais , Circovirus/genética , Genoma Viral/genética , Hibridização In Situ/veterinária , Masculino , Filogenia , Reação em Cadeia da Polimerase/veterinária , Serpentes/virologia
15.
Nat Microbiol ; 4(7): 1120-1128, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30936486

RESUMO

Commensal microbes profoundly impact host immunity to enteric viral infections1. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut2,3. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.


Assuntos
Infecções por Caliciviridae/prevenção & controle , Gastroenterite/prevenção & controle , Trato Gastrointestinal/virologia , Hospedeiro Imunocomprometido , Interferons/metabolismo , Norovirus/imunologia , Animais , Astroviridae/classificação , Astroviridae/genética , Astroviridae/isolamento & purificação , Astroviridae/fisiologia , Infecções por Caliciviridae/imunologia , Infecções por Caliciviridae/virologia , Transplante de Microbiota Fecal , Fezes/virologia , Feminino , Gastroenterite/imunologia , Gastroenterite/virologia , Trato Gastrointestinal/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Transdução de Sinais , Eliminação de Partículas Virais
16.
Int J Food Microbiol ; 299: 58-63, 2019 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-30954876

RESUMO

Bivalve molluscan shellfish, such as oysters, clams, and cockles, are well-recognized as vectors that concentrate foodborne pathogens by filter feeding. The objective of this study was to investigate the distribution and persistence of hepatitis A virus (HAV) in experimentally contaminated oysters that were either fed or not fed with algae. Oysters were experimentally contaminated with HAV and maintained in depuration conditions. qRT-PCR, immunohistochemistry (IHC), and in situ hybridization (ISH) were performed on oyster samples collected at 0, 1, 3, 5, and 7 days post-inoculation. When HAV-contaminated oysters were depurated for 7 days, HAV was detected in 91.1-97.8% of the digestive glands and gills. While the high viral load in the digestive glands in oysters did not change significantly regardless of algae-feeding, the viral load of the gills gradually decreased in both groups during the depuration. HAV antigen and RNA were detected in the digestive diverticula and connective tissues by both IHC and ISH. HAV was detected in the stomach, intestine, and gills by only ISH. The distribution of HAV in various oyster tissues may explain the persistence of contamination in oysters during the depuration process.


Assuntos
Microbiologia de Alimentos , Vírus da Hepatite A/fisiologia , Ostreidae/virologia , Animais , Manipulação de Alimentos , Trato Gastrointestinal/virologia , Brânquias/virologia , Vírus da Hepatite A/genética , Frutos do Mar/virologia , Fatores de Tempo
17.
PLoS Pathog ; 15(4): e1007709, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31017981

RESUMO

Norovirus infection is the leading cause of food-borne gastroenteritis worldwide, being responsible for over 200,000 deaths annually. Studies with murine norovirus (MNV) showed that protective STAT1 signaling controls viral replication and pathogenesis, but the immune mechanisms that noroviruses exploit to induce pathology are elusive. Here, we show that gastrointestinal MNV infection leads to widespread IL-1ß maturation in MNV-susceptible STAT1-deficient mice. MNV activates the canonical Nlrp3 inflammasome in macrophages, leading to maturation of IL-1ß and to Gasdermin D (GSDMD)-dependent pyroptosis. STAT1-deficient macrophages displayed increased MAVS-mediated expression of pro-IL-1ß, facilitating elevated Nlrp3-dependent release of mature IL-1ß upon MNV infection. Accordingly, MNV-infected Stat1-/- mice showed Nlrp3-dependent maturation of IL-1ß as well as Nlrp3-dependent pyroptosis as assessed by in vivo cleavage of GSDMD to its active N-terminal fragment. While MNV-induced diarrheic responses were not affected, Stat1-/- mice additionally lacking either Nlrp3 or GSDMD displayed lower levels of the fecal inflammatory marker Lipocalin-2 as well as delayed lethality after gastrointestinal MNV infection. Together, these results uncover new insights into the mechanisms of norovirus-induced inflammation and cell death, thereby revealing Nlrp3 inflammasome activation and ensuing GSDMD-driven pyroptosis as contributors to MNV-induced immunopathology in susceptible STAT1-deficient mice.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Infecções por Caliciviridae/patologia , Trato Gastrointestinal/patologia , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Fator de Transcrição STAT1/fisiologia , Animais , Proteínas Reguladoras de Apoptose/genética , Infecções por Caliciviridae/imunologia , Infecções por Caliciviridae/metabolismo , Infecções por Caliciviridae/virologia , Células Cultivadas , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/virologia , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Norovirus/imunologia , Norovirus/patogenicidade
18.
Virol Sin ; 34(3): 253-261, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30911896

RESUMO

Epstein-Barr virus (EBV) is an important human dsDNA virus, which has been shown to be associated with several malignancies including about 10% of gastric carcinomas. How EBV enters an epithelial cell has been an interesting project for investigation. "Cell-in-cell" infection was recently reported an efficient way for the entry of EBV into nasopharynx epithelial cells. The present approach was to explore the feasibility of this mode for EBV infection in gastric epithelial cells and the dynamic change of host inflammatory reaction. The EBV-positive lymphoblastic cells of Akata containing a GFP tag in the viral genome were co-cultured with the gastric epithelial cells (GES-1). The infection situation was observed under fluorescence and electron microscopies. Real-time quantitative PCR and Western-blotting assay were employed to detect the expression of a few specific cytokines and inflammatory factors. The results demonstrated that EBV could get into gastric epithelial cells by "cell-in-cell" infection but not fully successful due to the host fighting. IL-1ß, IL-6 and IL-8 played prominent roles in the cellular response to the infection. The activation of NF-κB and HSP70 was also required for the host antiviral response. The results imply that the gastric epithelial cells could powerfully resist the virus invader via cell-in-cell at the early stage through inflammatory and innate immune responses.


Assuntos
Formação de Célula em Célula , Células Epiteliais/virologia , Trato Gastrointestinal/virologia , Herpesvirus Humano 4/fisiologia , Linhagem Celular , Citocinas/imunologia , Células Epiteliais/imunologia , Fluorescência , Trato Gastrointestinal/citologia , Proteínas de Fluorescência Verde , Proteínas de Choque Térmico HSP72/metabolismo , Herpesvirus Humano 4/genética , Humanos , Imunidade Inata , Hibridização In Situ , Inflamação , Microscopia Eletrônica de Transmissão , NF-kappa B/metabolismo
19.
Int Rev Cell Mol Biol ; 345: 137-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30904192

RESUMO

The gut bacterial and fungal communities residing in the gastrointestinal tract have undisputed far-reaching effects in regulating host health. In the meantime, however, metagenomic sequencing efforts are revealing enteric viruses as the most abundant dimension of the intestinal gut ecosystem, and the first gut virome-wide association studies showed that inflammatory bowel disease as well as type 1 diabetes could be linked to the presence or absence of particular viral inhabitants in the intestine. In line with the genetic component of these human diseases, mouse model studies demonstrated how beneficial functions of a resident virus can switch to detrimental inflammatory effects in a genetically predisposed host. Such viral-induced intestinal immune disturbances are also recapitulated by several gastrointestinal infectious viruses such as rotavirus and human norovirus. This wide range of viral effects on intestinal immunity emphasizes the need for understanding the innate immune responses to gastrointestinal viruses. Numerous nucleic acid sensors such as DexD/H helicases and AIM2 serve as cytosolic viral guardians to induce antiviral interferon and/or pro-inflammatory inflammasome responses. In both cases, pioneering examples are emerging in which RNA helicases cooperate with particular Nod-like receptors to trigger these cellular responses to enteric viruses. Here we summarize the reported beneficial versus detrimental effects of enteric viruses in the intestinal immune system, and we zoom in on the mechanisms through which sensing of nucleic acids from these enteric viruses trigger interferon and inflammasome responses.


Assuntos
Trato Gastrointestinal/virologia , Inflamassomos/metabolismo , Interferons/metabolismo , Ácidos Nucleicos/farmacologia , Vírus/imunologia , Animais , Microbioma Gastrointestinal , Humanos
20.
J Virol Methods ; 268: 1-8, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30844408

RESUMO

In recent years, a series of porcine diarrhea viruses such as porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), rotaviruses of group A (RVA), rotaviruses of group C (RVC), and porcine circovirus 2 (PCV2) caused enormous economic losses all over the world. While any of these viruses is capable to cause disease alone, there is often concurrent infection with more than one virus on pig farms. In this study, a multiplex real-time PCR method based on EvaGreen fluorescent dye and melting curve analysis was established to simultaneously detect these five viruses in a single closed tube. Five distinct melt peaks were obtained with different melting temperature (Tm) value corresponding to each of the five viruses. This method was highly sensitive to detect and distinguish TGEV, RVA, RVC, PEDV and PCV2 with the limits of detection ranging from 5 to 50 copies/µL. The intra-assay and inter-assay reproducibility were good with coefficient of variation of Tm and cycle threshold values less than 0.32% and 2.86%, respectively. Testing of 90 field samples by the single and multiplex real-time PCR assays demonstrated a concordance of 91.1%. Thus, the EvaGreen multiplex real-time PCR is a rapid, sensitive and low-cost diagnostic tool for differential detection and routine surveillance of TGEV, RVA, RVC, PEDV and PCV2 in pigs.


Assuntos
Trato Gastrointestinal/virologia , Reação em Cadeia da Polimerase Multiplex , Doenças dos Suínos/virologia , Temperatura de Transição , Viroses/veterinária , Vírus/isolamento & purificação , Animais , Primers do DNA/genética , Diarreia/veterinária , Diarreia/virologia , Fezes/virologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos , Doenças dos Suínos/diagnóstico , Viroses/diagnóstico , Vírus/classificação
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