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1.
Front Immunol ; 12: 635471, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717181

RESUMO

COVID-19 is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and according to the World Health Organization (WHO), to date, SARS-CoV-2 has already infected more than 91.8 million people worldwide with 1,986,871 deaths. This virus affects mainly the respiratory system, but the gastrointestinal tract (GIT) is also a target, meanwhile SARS-CoV-2 was already detected in oesophagus, stomach, duodenum, rectum, and in fecal samples from COVID-19 patients. Prolonged GIT manifestations in COVID-19, mainly the diarrhea, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed SARS-CoV-2 clearance. So, the bidirectional interactions between the respiratory mucosa and the gut microbiota, known as gut-lung axis, are supposed to be involved in the healthy or pathologic immune responses to SARS-CoV-2. In accordance, the intestinal dysbiosis is associated with increased mortality in other respiratory infections, due to an exacerbated inflammation and decreased regulatory or anti-inflammatory mechanisms in the lungs and in the gut, pointing to this important relationship between both mucosal compartments. Therefore, since the mucous membranes from the respiratory and gastrointestinal tracts are affected, in addition to dysbiosis and inflammation, it is plausible to assume that adjunctive therapies based on the modulation of the gut microbiota and re-establishment of eubiosis conditions could be an important therapeutic approach for constraining the harmful consequences of COVID-19. Then, in this review, we summarized studies showing the persistence of SARS-CoV-2 in the gastrointestinal system and the related digestive COVID-19 manifestations, in addition to the literature demonstrating nasopharyngeal, pulmonary and intestinal dysbiosis in COVID-19 patients. Lastly, we showed the potential beneficial role of probiotic administration in other respiratory infections, and discuss the possible role of probiotics as an adjunctive therapy in SARS-CoV-2 infection.


Assuntos
/microbiologia , Intestinos/microbiologia , Pulmão/microbiologia , /fisiologia , /terapia , Disbiose , Microbioma Gastrointestinal , Humanos , Intestinos/virologia , Pulmão/virologia , Probióticos
2.
Stem Cell Reports ; 16(3): 493-504, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33626333

RESUMO

Enteroviruses, such as EV-A71 and CVA16, mainly infect the human gastrointestinal tract. Human coronaviruses, including SARS-CoV and SARS-CoV-2, have been variably associated with gastrointestinal symptoms. We aimed to optimize the human intestinal organoids and hypothesize that these optimized intestinal organoids can recapitulate enteric infections of enterovirus and coronavirus. We demonstrate that the optimized human intestinal organoids enable better simulation of the native human intestinal epithelium, and that they are significantly more susceptible to EV-A71 than CVA16. Higher replication of EV-A71 than CVA16 in the intestinal organoids triggers a more vigorous cellular response. However, SARS-CoV and SARS-CoV-2 exhibit distinct dynamics of virus-host interaction; more robust propagation of SARS-CoV triggers minimal cellular response, whereas, SARS-CoV-2 exhibits lower replication capacity but elicits a moderate cellular response. Taken together, the disparate profile of the virus-host interaction of enteroviruses and coronaviruses in human intestinal organoids may unravel the cellular basis of the distinct pathogenicity of these viral pathogens.


Assuntos
/virologia , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/virologia , Intestinos/virologia , Organoides/virologia , /patogenicidade , Animais , Linhagem Celular , Chlorocebus aethiops , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Mucosa Intestinal/virologia , Células Vero , Replicação Viral/fisiologia
3.
Nat Commun ; 12(1): 134, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420022

RESUMO

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.


Assuntos
/metabolismo , /transmissão , Ácidos Siálicos/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Ligação Viral , Animais , Células CACO-2 , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetinae , Furina/metabolismo , Células HEK293 , Heparitina Sulfato/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestinos/virologia , Pulmão/patologia , Pulmão/virologia , Síndrome Respiratória Aguda Grave/patologia , Células Vero , Internalização do Vírus , Replicação Viral/fisiologia
4.
Int J Food Microbiol ; 340: 109058, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33461001

RESUMO

Bivalve molluscan shellfish such as oysters are filter feeders and are able to accumulate human noroviruses (NoVs) largely due to the presence of human histo-blood group antigens (HBGAs)-like carbohydrates in their intestine. Since the fucose contents play a key role in the binding of NoVs to HBGAs, this study intended to investigate the influence of fucosidase-producing bifidobacteria on the HBGA antigenicity of oyster digestive tissue and the associated NoV binding. On the contrary to the expected, after a treatment of the oyster digestive tissue extracts with Bifidobacterium bifidum strain JCM 1254, the binding of human NoV GII.4 virus like particles (VLPs) to the oyster digestive tissue extracts enhanced significantly (OD450 from 1.15 ± 0.05 to 1.51 ± 0.02, P < 0.001) in an in vitro direct binding assay. The accumulation of human NoV GII·P16-GII.4 also enhanced significantly in the intestine of B. bifidum JCM 1254 treated oysters from 4.27 ± 0.25 log genomic copies/g oyster digestive tissue to 5.25 ± 0.29 log genomic copies/g oyster digestive tissue (P < 0.005) as observed in an in vivo test. Correspondingly, the type A antigenicity of the oyster digestive tissue extracts enhanced (OD450 from 0.77 ± 0.04 to 1.06 ± 0.05, P < 0.01) after the treatment with B. bifidum JCM 1254. These results could be explained by the substrate specificity of the B. bifidum JCM 1254 associated fucosidases. This study identified an indirect interaction possibly happening between the bacterial microbiota with human NoVs during their transmission in the food systems. We also supplied a potential strategy to mitigate the NoV contamination from shellfish, suppose bacterial strains with specified fucosidase production could be obtained in the future.


Assuntos
Bifidobacterium/enzimologia , Antígenos de Grupos Sanguíneos/metabolismo , Norovirus/metabolismo , Ostreidae/virologia , Frutos do Mar/virologia , alfa-L-Fucosidase/metabolismo , Animais , Anticorpos Monoclonais , Bifidobacterium/fisiologia , Antígenos de Grupos Sanguíneos/imunologia , Humanos , Intestinos/imunologia , Intestinos/virologia , Ostreidae/imunologia
5.
Viruses ; 13(2)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494515

RESUMO

Norovirus is the leading cause of acute gastroenteritis worldwide. The pathogenesis of norovirus and the induced immune response remain poorly understood due to the lack of a robust virus culture system. The monolayers of two secretor-positive Chinese human intestinal enteroid (HIE) lines were challenged with two norovirus pandemic GII.4 Sydney strains. Norovirus RNA replication in supernatants and cell lysates were quantified by RT-qPCR. RNA expression levels of immune-related genes were profiled using PCR arrays. The secreted protein levels of shortlisted upregulated genes were measured in supernatants using analyte-specific enzyme-linked immunosorbent assay (ELISA). Productive norovirus replications were achieved in three (75%) out of four inoculations. The two most upregulated immune-related genes were CXCL10 (93-folds) and IFI44L (580-folds). Gene expressions of CXCL10 and IFI44L were positively correlated with the level of norovirus RNA replication (CXCL10: Spearman's r = 0.779, p < 0.05; IFI44L: r = 0.881, p < 0.01). The higher level of secreted CXCL10 and IFI44L proteins confirmed their elevated gene expression. The two genes have been reported to be upregulated in norovirus volunteer challenges and natural human infections by other viruses. Our data suggested that HIE could mimic the innate immune response elicited in natural norovirus infection and, therefore, could serve as an experimental model for future virus-host interaction and antiviral studies.


Assuntos
Infecções por Caliciviridae/imunologia , Quimiocina CXCL10/metabolismo , Intestinos/virologia , Proteínas Supressoras de Tumor/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular , Quimiocina CXCL10/genética , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Imunidade Inata , Interferons/genética , Interferons/metabolismo , Intestinos/imunologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Norovirus/patogenicidade , Norovirus/fisiologia , Organoides/imunologia , Organoides/virologia , Análise de Sequência de RNA , Proteínas Supressoras de Tumor/genética , Replicação Viral
6.
Int J Mol Sci ; 22(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498321

RESUMO

The gut microbiota has emerged as a key factor in the pathogenesis of intestinal viruses, including enteroviruses, noroviruses and rotaviruses (RVs), where stimulatory and inhibitory effects on infectivity have been reported. With the aim of determining whether members of the microbiota interact with RVs during infection, a combination of anti-RV antibody labeling, fluorescence-activated cell sorting and 16S rRNA amplicon sequencing was used to characterize the interaction between specific bacteria and RV in stool samples of children suffering from diarrhea produced by G1P[8] RV. The genera Ruminococcus and Oxalobacter were identified as RV binders in stools, displaying enrichments between 4.8- and 5.4-fold compared to samples nonlabeled with anti-RV antibodies. In vitro binding of the G1P[8] Wa human RV strain to two Ruminococcus gauvreauii human isolates was confirmed by fluorescence microscopy. Analysis in R. gauvreauii with antibodies directed to several histo-blood group antigens (HBGAs) indicated that these bacteria express HBGA-like substances on their surfaces, which can be the target for RV binding. Furthermore, in vitro infection of the Wa strain in differentiated Caco-2 cells was significantly reduced by incubation with R. gauvreauii. These data, together with previous findings showing a negative correlation between Ruminococcus levels and antibody titers to RV in healthy individuals, suggest a pivotal interaction between this bacterial group and human RV. These results reveal likely mechanisms of how specific bacterial taxa of the intestinal microbiota could negatively affect RV infection and open new possibilities for antiviral strategies.


Assuntos
Microbioma Gastrointestinal , Infecções por Rotavirus/microbiologia , Rotavirus/metabolismo , Ruminococcus/metabolismo , Proteínas de Bactérias/metabolismo , Células CACO-2 , Pré-Escolar , Humanos , Intestinos/microbiologia , Intestinos/virologia , Ligação Proteica , Rotavirus/patogenicidade , Infecções por Rotavirus/virologia , Ruminococcus/patogenicidade
7.
Viruses ; 13(1)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477379

RESUMO

Porcine deltacoronavirus (PDCoV) strain OH-FD22 infects poultry and shares high nucleotide identity with sparrow-origin deltacoronaviruses (SpDCoV) ISU73347 and HKU17 strains. We hypothesized that the spike (S) protein or receptor-binding domain (RBD) from these SpDCoVs would alter the host and tissue tropism of PDCoV. First, an infectious cDNA clone of PDCoV OH-FD22 strain (icPDCoV) was generated and used to construct chimeric icPDCoVs harboring the S protein of HKU17 (icPDCoV-SHKU17) or the RBD of ISU73347 (icPDCoV-RBDISU). To evaluate their pathogenesis, neonatal gnotobiotic pigs were inoculated orally/oronasally with the recombinant viruses or PDCoV OH-FD22. All pigs inoculated with icPDCoV or OH-FD22 developed severe diarrhea and shed viral RNA at moderate-high levels (7.62-10.56 log10 copies/mL) in feces, and low-moderate levels in nasal swabs (4.92-8.48 log10 copies/mL). No pigs in the icPDCoV-SHKU17 and icPDCoV-RBDISU groups showed clinical signs. Interestingly, low-moderate levels (5.07-7.06 log10 copies/mL) of nasal but not fecal viral RNA shedding were detected transiently at 1-4 days post-inoculation in 40% (2/5) of icPDCoV-SHKU17- and 50% (1/2) of icPDCoV-RBDISU-inoculated pigs. These results confirm that PDCoV infected both the upper respiratory and intestinal tracts of pigs. The chimeric viruses displayed an attenuated phenotype with the loss of tropism for the pig intestine. The SpDCoV S protein and RBD reduced viral replication in pigs, suggesting limited potential for cross-species spillover upon initial passage.


Assuntos
Infecções por Coronavirus/patologia , Intestinos/patologia , Sistema Respiratório/patologia , Glicoproteína da Espícula de Coronavírus/genética , Tropismo Viral/genética , Motivos de Aminoácidos , Animais , Doenças das Aves/virologia , Linhagem Celular , Intestinos/virologia , Proteínas Recombinantes/genética , Sistema Respiratório/virologia , Pardais , Suínos , Doenças dos Suínos/virologia , Virulência/genética
8.
J Vet Sci ; 21(5): e80, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33016025

RESUMO

BACKGROUND: In suckling piglets, transmissible gastroenteritis virus (TGEV) causes lethal diarrhea accompanied by high infection and mortality rates, leading to considerable economic losses. This study explored methods of preventing or inhibiting their production. Bovine antimicrobial peptide-13 (APB-13) has antibacterial, antiviral, and immune functions. OBJECTIVES: This study analyzed the efficacy of APB-13 against TGEV through in vivo and in vitro experiments. METHODS: The effects of APB-13 toxicity and virus inhibition rate on swine testicular (ST) cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT). The impact of APB-13 on virus replication was examined through the 50% tissue culture infective dose (TCID50). The mRNA and protein levels were investigated by real-time quantitative polymerase chain reaction and western blot (WB). Tissue sections were used to detect intestinal morphological development. RESULTS: The safe and effective concentration range of APB-13 on ST cells ranged from 0 to 62.5 µg/mL, and the highest viral inhibitory rate of APB-13 was 74.1%. The log10TCID50 of 62.5 µg/mL APB-13 was 3.63 lower than that of the virus control. The mRNA and protein expression at 62.5 µg/mL APB-13 was significantly lower than that of the virus control at 24 hpi. Piglets in the APB-13 group showed significantly lower viral shedding than that in the virus control group, and the pathological tissue sections of the jejunum morphology revealed significant differences between the groups. CONCLUSIONS: APB-13 exhibited good antiviral effects on TGEV in vivo and in vitro.


Assuntos
Antivirais/farmacologia , Gastroenterite Suína Transmissível/tratamento farmacológico , Vírus da Gastroenterite Transmissível/efeitos dos fármacos , Animais , Western Blotting/veterinária , Células Cultivadas , Intestinos/virologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Suínos
9.
Proc Natl Acad Sci U S A ; 117(38): 23782-23793, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32907944

RESUMO

Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis worldwide; yet currently, no vaccines or FDA-approved antiviral drugs are available to counter these pathogens. To understand HuNoV biology and the epithelial response to infection, we performed transcriptomic analyses, RT-qPCR, CRISPR-Cas9 modification of human intestinal enteroid (HIE) cultures, and functional studies with two virus strains (a pandemic GII.4 and a bile acid-dependent GII.3 strain). We identified a predominant type III interferon (IFN)-mediated innate response to HuNoV infection. Replication of both strains is sensitive to exogenous addition of IFNs, suggesting the potential of IFNs as therapeutics. To obtain insight into IFN pathway genes that play a role in the antiviral response to HuNoVs, we developed knockout (KO) HIE lines for IFN alpha and lambda receptors and the signaling molecules, MAVS, STAT1, and STAT2 An unexpected differential response of enhanced replication and virus spread was observed for GII.3, but not the globally dominant GII.4 HuNoV in STAT1-knockout HIEs compared to parental HIEs. These results indicate cellular IFN responses restrict GII.3 but not GII.4 replication. The strain-specific sensitivities of innate responses against HuNoV replication provide one explanation for why GII.4 infections are more widespread and highlight strain specificity as an important factor in HuNoV biology. Genetically modified HIEs for innate immune genes are useful tools for studying immune responses to viral or microbial pathogens.


Assuntos
Infecções por Caliciviridae , Interações Hospedeiro-Patógeno/imunologia , Interferons , Intestinos , Norovirus , Sistemas CRISPR-Cas , Infecções por Caliciviridae/imunologia , Infecções por Caliciviridae/virologia , Humanos , Interferons/genética , Interferons/metabolismo , Intestinos/imunologia , Intestinos/virologia , Modelos Biológicos , Norovirus/genética , Norovirus/imunologia , Norovirus/patogenicidade , Organoides/imunologia , Organoides/virologia , Análise de Sequência de RNA , Transcriptoma/genética , Replicação Viral
11.
Vet Microbiol ; 247: 108785, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32768229

RESUMO

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea, vomiting and mortality in nursing piglets. Type III interferons (IFN-λs) are the major antiviral cytokines in intestinal epithelial cells, the target cells in vivo for PDCoV. In this study, we found that PDCoV infection remarkably inhibited Sendai virus-induced IFN-λ1 production by suppressing transcription factors IRF and NF-κB in IPI-2I cells, a line of porcine intestinal mucosal epithelial cells. We also confirmed that PDCoV infection impeded the activation of IFN-λ1 promoter stimulated by RIG-I, MDA5 and MAVS, but not by TBK1 and IRF1. Although the expression levels of IRF1 and MAVS were not changed, PDCoV infection resulted in reduction of the number of peroxisomes, the platform for MAVS to activate IRF1, and subsequent type III IFN production. Taken together, our study demonstrates that PDCoV suppresses type III IFN responses to circumvent the host's antiviral immunity.


Assuntos
Infecções por Coronavirus/veterinária , Células Epiteliais/imunologia , Células Epiteliais/virologia , Interações Hospedeiro-Patógeno/imunologia , Interferons/antagonistas & inibidores , Animais , Linhagem Celular , Coronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Fator Regulador 1 de Interferon/antagonistas & inibidores , Fator Regulador 1 de Interferon/imunologia , Interferons/imunologia , Intestinos/citologia , Intestinos/virologia , Rim/citologia , Rim/virologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Vírus Sendai/imunologia , Transdução de Sinais/imunologia , Suínos/virologia , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia
12.
Gastroenterol Hepatol ; 43(8): 464-471, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32859408

RESUMO

The SARS-CoV-2 pandemic is leading to high mortality and a global health crisis. The primary involvement is respiratory; however, the virus can also affect other organs, such as the gastrointestinal tract and liver. The most common symptoms are anorexia and diarrhea. In about half of the cases, viral RNA could be detected in the stool, which is another line of transmission and diagnosis. covid19 has a worse prognosis in patients with comorbidities, although there is not enough evidence in case of previous digestive diseases. Digestive endoscopies may give rise to aerosols, which make them techniques with a high risk of infection. Experts and scientific organizations worldwide have developed guidelines for preventive measures. The available evidence on gastrointestinal and hepatic involvement, the impact on patients with previous digestive diseases and operating guidelines for Endoscopy Units during the pandemic are reviewed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Doenças do Sistema Digestório/etiologia , Sistema Digestório/virologia , Pandemias , Pneumonia Viral/complicações , Aerossóis , Anorexia/etiologia , Antivirais/efeitos adversos , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Estudos de Coortes , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Diarreia/etiologia , Doenças do Sistema Digestório/virologia , Endoscopia do Sistema Digestório/efeitos adversos , Fezes/virologia , Humanos , Imunossupressores/efeitos adversos , Intestinos/química , Intestinos/virologia , Hepatopatias/etiologia , Estudos Multicêntricos como Assunto , Pandemias/prevenção & controle , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/fisiologia , Equipamento de Proteção Individual , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Receptores Virais/análise , Receptores Virais/fisiologia , Risco , Precauções Universais
13.
Arch Virol ; 165(10): 2323-2333, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32715325

RESUMO

To investigate the epidemic characteristics of porcine epidemic diarrhea virus (PEDV), 135 clinical samples (including intestinal tissues and feces) were collected from diseased piglets during outbreaks of diarrhea from 2015 to 2019 on farms in Henan and Shanxi provinces of China where swine had been immunized with attenuated PEDV (CV777). A total of 86 clinical samples (86/135, 63.7%) were positive for PEDV by RT-PCR, and subsequently, the complete spike (S) and ORF3 genes of 32 PEDV samples were sequenced. Phylogenetic analysis showed that the 32 PEDV strains obtained in this study belonged to group 2 (pandemic variant strains) and had a close relationship to 17 Chinese strains after 2010, two South Korean strains (KNU-1305 and KNU-1807), three American strains (PC22A-P140.BI, USA/Colorado/2013, and USA/OK10240-6/2017) and a Mexican strain (PEDV/MEX/QRO/02/2017), but differed genetically from a South Korean strain (SM98), a European strain (Br1/87), a Chinese strain (LZC), and a vaccine strain (CV777). G2-a subgroup strains were the dominant pandemic variant strains circulating in Henan and Shanxi provinces of China. Furthermore, a cross-recombination event was identified in the S region of the SX/TY2/2017 strain, and the putative parental strains were the epidemic strains CH/GDGZ/2012 and CH/YZ1/2015, identified in China in 2012 and 2015, respectively. These results provide further information about PEDV evolution, which could improve our understanding of the circulation of PEDV in Henan and Shanxi provinces. This information will also be helpful for developing new strategies for prevention and control of variant strains.


Assuntos
Infecções por Coronavirus/veterinária , Diarreia/veterinária , Surtos de Doenças , Genoma Viral , Vírus da Diarreia Epidêmica Suína/genética , Glicoproteína da Espícula de Coronavírus/genética , Doenças dos Suínos/epidemiologia , Proteínas Virais/genética , Animais , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Diarreia/epidemiologia , Diarreia/virologia , Fazendas , Fezes/virologia , Variação Genética , Intestinos/virologia , Filogenia , Vírus da Diarreia Epidêmica Suína/classificação , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Recombinação Genética , Suínos/virologia , Doenças dos Suínos/transmissão , Doenças dos Suínos/virologia
14.
Med Hypotheses ; 143: 110116, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32721808

RESUMO

The pandemic of acute respiratory illness caused by the novel betacoronavirus SARS-CoV-2, officially designated COVID-19, has attained the proportions of a global health crisis. Though all nations of the world have been affected by this disease, there have been marked cross-national variations in prevalence, severity and mortality rates. Various explanations, based on demographic, social and climatic factors, have been suggested to account for this variability, but these remain unverified to date. Based on recent research findings suggesting that human enterocytes may serve as a point of entry for SARS-CoV-2, leading to intestinal viral replication, this paper puts forward the hypothesis that prior intestinal infection with coronaviruses, either symptomatic or asymptomatic, may moderate this process and minimize the severity of SARS-CoV-2 infection. This hypothesis is supported by evidence on the gastrointestinal manifestations of SARS-CoV-2 and related infections, on the geographical patterns observed in the variability of COVID-19 mortality, and on the occurrence and geographical distribution of outbreaks of diarrheal disease, as well as asymptomatic infection, with human coronaviruses as verified by direct or serological testing. Preliminary supporting evidence based on national and international health statistics is presented, along with suggestions on more robust methods by which this hypothesis may be tested. If the proposal put forth in this paper can be confirmed either wholly or in part, it would have significant implications in terms of strategies aimed at minimizing the severity of COVID-19 in a clinical setting.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Diarreia/imunologia , Modelos Imunológicos , Pandemias , Pneumonia Viral/imunologia , Adulto , Anticorpos Antivirais/imunologia , Criança , Pré-Escolar , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Reações Cruzadas , Diarreia/microbiologia , Diarreia/virologia , Diarreia Infantil/imunologia , Diarreia Infantil/virologia , Resistência à Doença , Células Epiteliais/virologia , Fezes/virologia , Microbioma Gastrointestinal , Saúde Global , Humanos , Lactente , Intestinos/virologia , Pneumonia Viral/mortalidade , Pneumonia Viral/transmissão , Anos de Vida Ajustados por Qualidade de Vida
15.
Pediatr. aten. prim ; 22(86): 189-194, abr.-jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-187743

RESUMO

Desde la aparición de los primeros casos en diciembre de 2019 hasta el momento actual, más de tres millones de personas se han infectado por SARS-CoV-2 en el mundo. Los síntomas más frecuentes son fiebre, tos, mialgias y dificultad respiratoria. No obstante, al progresar la pandemia, se ha prestado una atención creciente a los síntomas gastrointestinales. Entre ellos, destacan hiporexia, náuseas, vómitos y diarrea. También puede haber hipertransaminasemia. Desde el punto de vista digestivo, cabe tener en cuenta que ciertas patologías crónicas, como la enfermedad inflamatoria intestinal, pueden beneficiarse de ciertas modificaciones en cuanto a tratamiento se refiere. Por último, cabe reflejar que ha de extremarse la precaución durante la realización de endoscopias. En esta revisión se ahonda en todos estos aspectos


From the beginning of the pandemic to the current moment, more than three million people have been infected with SARS-CoV-2 in the world. The most frequent symptoms are fever, cough, myalgia and respiratory distress. However, as the pandemic progresses, more gastrointestinal symptoms have been notified. Among them, hiporexia, nausea, vomiting and diarrhea. There may also be hipertransaminasemia. Patients with inflammatory bowel disease may be benefited by certain treatment modifications. Caution should be exercised during endoscopies. All of these topics are discussed in this review


Assuntos
Humanos , Infecções por Coronavirus/diagnóstico , Vírus da SARS/patogenicidade , Doenças Inflamatórias Intestinais/complicações , Intestinos/virologia , Infecções por Coronavirus/fisiopatologia , Vômito/epidemiologia , Diarreia/epidemiologia , Anorexia/epidemiologia , Endoscopia Gastrointestinal/normas , Hemorragia Gastrointestinal/epidemiologia , Dor Abdominal/epidemiologia
16.
PLoS One ; 15(5): e0233557, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442222

RESUMO

Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial species diversity and biochemical cycles. We performed a prospective, case-control study on children with CF and age and gender matched healthy controls (HC), to investigate the composition and function of intestinal viral communities. Stool samples were enriched for viral DNA and RNA by viral extraction, random amplification and purification before sequencing (Illumina MiSeq). Taxonomic assignment of viruses was performed using Vipie. Functional annotation was performed using Virsorter. Inflammation was measured by calprotectin and M2-pyruvate kinase (M2-PK). Eight CF and eight HC subjects were included (50% male, mean age 6.9 ± 3.0 and 6.4 ± 5.3 years, respectively, p = 0.8). All CF subjects were pancreatic insufficient. Regarding the intestinal virome, no difference in Shannon index between CF and HC was identified. Taxonomy-based beta-diversity (presence-absence Bray-Curtis dissimilarity) was significantly different between CF and HC (R2 = 0.12, p = 0.001). Myoviridae, Faecalibacterium phage FP Taranis and unclassified Gokushovirinae were significantly decreased in CF compared with HC (q<0.05). In children with CF (compared to HC), the relative abundance of genes annotated to (i) a peptidoglycan-binding domain of the peptidoglycan hydrolases (COG3409) was significantly increased (q<0.05) and (ii) capsid protein (F protein) (PF02305.16) was significantly decreased (q<0.05). Picornavirales, Picornaviridae, and Enterovirus were found to positively correlate with weight and BMI (r = 0.84, q = 0.01). Single-stranded DNA viruses negatively correlated with M2-PK (r = -0.86, q = 0.048). Children with CF have an altered intestinal virome compared to well-matched HC, with both taxonomic and predicted functional changes. Further exploration of Faecalibacterium phages, Gokushovirinae and phage lysins are warranted. Intestinal viruses and their functions may have important clinical implications for intestinal inflammation and growth in children with CF, potentially providing novel therapeutic targets.


Assuntos
Fibrose Cística/virologia , Disbiose/virologia , Insuficiência Pancreática Exócrina/virologia , Inflamação/virologia , Intestinos/virologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Fezes/virologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Vírus/classificação , Vírus/isolamento & purificação
17.
Am J Trop Med Hyg ; 103(2): 869-875, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32431284

RESUMO

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are arthropod-borne viruses transmitted mainly by Aedes aegypti mosquitoes. These viruses have become endemic in large parts of North, Central, and South America. Arboviruses persistently infect mosquitoes throughout their life span and become infectious (i.e., expectorate infectious virus in saliva) after a period of time called the extrinsic incubation period (EIP). The duration of this infectiousness, however, is not well characterized. This is an important shortcoming because many epidemiological models assume that mosquitoes continue to be infectious for the duration of their life span. To define the duration of infectiousness for CHIKV and ZIKV, mosquitoes were infected orally with these viruses. Every 2 days, legs/wings, midguts, salivary glands, and saliva were collected from 30 to 60 mosquitoes and viral load measured. In CHIKV-infected mosquitoes, infectious virus in saliva peaked early (2-4 dpi), and then decreased rapidly and was rarely observed after 10 dpi. Viral RNA in infected tissues also decreased after the initial peak (4-8 dpi) but did so much less drastically. In ZIKV-infected mosquitoes, the infectious virus in saliva peaked at 12-14 dpi and dropped off only slightly after 14 dpi. In infected tissues, viral RNA increased early during infection, and then plateaued after 6-10 days. Our findings suggest that significant variation exists in the duration of the infectious period for arboviruses that is in part influenced by virus clearance from expectorated saliva.


Assuntos
Aedes/virologia , Vírus Chikungunya/fisiologia , Intestinos/virologia , Saliva/virologia , Glândulas Salivares/virologia , Replicação Viral/fisiologia , Zika virus/fisiologia , Animais , Febre de Chikungunya/transmissão , Extremidades/virologia , Período de Incubação de Doenças Infecciosas , Mosquitos Vetores/virologia , Asas de Animais/virologia , Infecção por Zika virus/transmissão
18.
Nat Med ; 26(7): 1077-1083, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32405028

RESUMO

A novel coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally1,2. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats1,2. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicus species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection3,4. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Intestinos/virologia , Organoides/virologia , Pneumonia Viral/patologia , Pneumonia Viral/transmissão , Animais , Diferenciação Celular , Células Cultivadas , Pré-Escolar , Quirópteros/virologia , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Enterócitos/patologia , Enterócitos/fisiologia , Enterócitos/virologia , Feminino , Humanos , Lactente , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Intestinos/patologia , Masculino , Organoides/patologia , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Vero , Carga Viral/genética , Carga Viral/métodos , Tropismo Viral/fisiologia
19.
Parasit Vectors ; 13(1): 188, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276649

RESUMO

BACKGROUND: Vector-borne diseases are a major public health concern and cause significant morbidity and mortality. Zika virus (ZIKV) is the etiologic agent of a massive outbreak in the Americas that originated in Brazil in 2015 and shows a strong association with congenital ZIKV syndrome in newborns. Cache Valley virus (CVV) is a bunyavirus that causes mild to severe illness in humans and ruminants. In this study, we investigated the vector competence of Virginia mosquitoes for ZIKV and CVV to explore their abilities to contribute to potential outbreaks. METHODS: To determine vector competence, mosquitoes were fed a blood meal comprised of defibrinated sheep blood and virus. The presence of midgut or salivary gland barriers to ZIKV infection were determined by intrathoracic inoculation vs oral infection. After 14-days post-exposure, individual mosquitoes were separated into bodies, legs and wings, and saliva expectorant. Virus presence was detected by plaque assay to determine midgut infection, dissemination, and transmission rates. RESULTS: Transmission rates for Ae. albopictus orally infected (24%) and intrathoracically inoculated (63%) with ZIKV was similar to Ae. aegypti (48% and 71%, respectively). Transmission rates of ZIKV in Ae. japonicus were low, and showed evidence of a midgut infection barrier demonstrated by low midgut infection and dissemination rates from oral infection (3%), but increased transmission rates after intrathoracic inoculation (19%). Aedes triseriatus was unable to transmit ZIKV following oral infection or intrathoracic inoculation. CVV transmission was dose-dependent where mosquitoes fed high titer (ht) virus blood meals developed higher rates of midgut infection, dissemination, and transmission compared to low titer (lt) virus blood meals. CVV was detected in the saliva of Ae. albopictus (ht: 68%, lt: 24%), Ae. triseriatus (ht: 52%, lt: 7%), Ae. japonicus (ht: 22%, lt: 0%) and Ae. aegypti (ht: 10%; lt: 7%). Culex pipiens and Cx. restuans were not competent for ZIKV or CVV. CONCLUSIONS: This laboratory transmission study provided further understanding of potential ZIKV and CVV transmission cycles with Aedes mosquitoes from Virginia. The ability for these mosquitoes to transmit ZIKV and CVV make them a public health concern and suggest targeted control programs by mosquito and vector abatement districts.


Assuntos
Vírus Bunyamwera/isolamento & purificação , Mosquitos Vetores/virologia , Zika virus/isolamento & purificação , Aedes/virologia , Animais , Bioensaio , Sangue/virologia , Infecções por Bunyaviridae/transmissão , Culex/virologia , Vetores de Doenças , Humanos , Intestinos/virologia , Saliva/virologia , Estados Unidos , Carga Viral , Virginia , Infecção por Zika virus/transmissão
20.
Avian Dis ; 64(1): 23-35, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32267122

RESUMO

An infectious bronchitis virus (IBV) with an unusual enteric tropism (CalEnt) was isolated from a California broiler flock exhibiting runting-stunting syndrome. IBV was detected in the small intestine, but not in the respiratory tract or kidney. During virus isolation in embryos, it did not replicate in chorioallantoic membrane (CAM) but could be recovered from intestines. Its S1 protein showed 93% amino acid sequence identity to a California variant isolated in 1999 (Cal99). Intestinal lesions were reproduced following ocular/nasal inoculation of specific-pathogen-free chickens, but respiratory signs and lesions were also present. The virus was detected in both respiratory and intestinal tissues. To determine whether the novel tropism of IBV CalEnt was due to an increased ability of its S1 protein to bind to the intestinal epithelium, we compared the binding of soluble trimeric recombinant S1 proteins derived from CalEnt and Cal99 to chicken tissues. Contrary to expectations, the CalEnt S1 protein did not bind to small intestine and, unlike Cal99 S1, did not bind to the respiratory epithelium or CAM. Using only the CalEnt S1 N-terminal domain or including the S2 ectodomain (lacking membrane and cytoplasmic domains), which have been shown to improve ArkDPI S1 protein binding, did not lead to detectable binding at the standard protein concentration to any tissue tested. Our results indicate no/poor binding of the CalEnt spike protein to both respiratory and intestinal tissues and thus do not support better attachment to intestinal epithelial cells as a reason for CalEnt's extended tropism. These results might reflect shortcomings of the assay, including that it does not detect potential contributions of the S1 C-terminal domain to attachment. We used bioinformatic approaches to explore the possibility that the unique tropism of CalEnt might be a result of functions of the S protein in cell-entry steps subsequent to attachment. These analyses suggest that CalEnt's S2 coding region was acquired through a recombination event and encodes a unique amino acid sequence at the putative recognition site for the protease that activates the S protein for fusion. Thus, S2 activation by tissue-specific proteases might facilitate CalEnt entry into intestinal epithelial cells and compensate for poor binding by its S1 protein.


Assuntos
Galinhas , Infecções por Coronavirus/veterinária , Vírus da Bronquite Infecciosa/fisiologia , Intestinos/virologia , Doenças das Aves Domésticas/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Tropismo Viral , Animais , California , Infecções por Coronavirus/virologia , Ligação Proteica
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