Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Influenza A virus infection induces liver injury in mice.

ABSTRACT: Respiratory infections such as SARS-CoV in humans are often accompanied by mild and self-limiting hepatitis. As a respiratory disease, influenza A virus (IAV) infection can lead to hepatitis, but the mechanism remains unclear. This study aimed to investigate the occurrence of hepatitis by establishing a model for infected mice for three different subtypes of respiratory IAVs (H1N1, H5N1, and H7N2). Histological analysis was performed, and results showed increase serum aminotransferase (ALT and AST) levels and evident liver injury on days 3 and 7, especially on day 5 post infection. Immunohistochemistry (IHC) results indicated a wide distribution of IAV's positive signals in the liver of infected mice. Real-time PCR results further revealed a similar viral titer to IHC that presented a remarkedly positive correlation with histology injury. All these data showed that the mouse model suitably contributed valuable information about the mechanism underlying the occurrence of hepatitis induced by respiratory influenza virus.

SUBMITTER: Zhang S

PROVIDER: S-EPMC7125922 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Influenza A virus infection induces liver injury in mice.

Zhang Shouping S Hu Bin B Xu Jingfei J Ren Qiuxuan Q Wang Lirong L Wang Sanhu S

Microbial pathogenesis 20190907

Respiratory infections such as SARS-CoV in humans are often accompanied by mild and self-limiting hepatitis. As a respiratory disease, influenza A virus (IAV) infection can lead to hepatitis, but the mechanism remains unclear. This study aimed to investigate the occurrence of hepatitis by establishing a model for infected mice for three different subtypes of respiratory IAVs (H1N1, H5N1, and H7N2). Histological analysis was performed, and results showed increase serum aminotransferase (ALT and A ...[more]

PMID: 31505263

Similar Datasets

Visualizing influenza virus infection in living mice.

Project description:Preventing and treating influenza virus infection remain a challenge because of incomplete understanding of the host-pathogen interactions, limited therapeutics and lack of a universal vaccine. So far, methods for monitoring the course of infection with influenza virus in real time in living animals are lacking. Here we report the visualization of influenza viral infection in living mice using an engineered replication-competent influenza A virus carrying luciferase reporter gene. After intranasal inoculation, bioluminescence can be detected in the chest and nasopharyngeal passage of living mice. The intensity of bioluminescence in the chest correlates with the dosage of infection and the viral load in the lung. Bioluminescence in the chest of infected mice diminishes on antiviral treatment. This work provides a novel approach that enables real-time study of influenza virus infection and effects of antiviral therapeutics in living animals.

| S-EPMC3778511 | biostudies-other

Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation.

Project description:Influenza in humans is often accompanied by gastroenteritis-like symptoms such as diarrhea, but the underlying mechanism is not yet understood. We explored the occurrence of gastroenteritis-like symptoms using a mouse model of respiratory influenza infection. We found that respiratory influenza infection caused intestinal injury when lung injury occurred, which was not due to direct intestinal viral infection. Influenza infection altered the intestinal microbiota composition, which was mediated by IFN-γ produced by lung-derived CCR9(+)CD4(+) T cells recruited into the small intestine. Th17 cells markedly increased in the small intestine after PR8 infection, and neutralizing IL-17A reduced intestinal injury. Moreover, antibiotic depletion of intestinal microbiota reduced IL-17A production and attenuated influenza-caused intestinal injury. Further study showed that the alteration of intestinal microbiota significantly stimulated IL-15 production from intestinal epithelial cells, which subsequently promoted Th17 cell polarization in the small intestine in situ. Thus, our findings provide new insights into an undescribed mechanism by which respiratory influenza infection causes intestinal disease.

| S-EPMC4235643 | biostudies-literature

A mouse monoclonal antibody against influenza C virus attenuates acetaminophen-induced liver injury in mice.

Project description:Molecular mimicry is one of the main processes for producing autoantibodies during infections. Although some autoantibodies are associated with autoimmune diseases, the functions of many autoantibodies remain unknown. Previously, we reported that S16, a mouse (BALB/c) monoclonal antibody against the hemagglutinin-esterase fusion glycoprotein of influenza C virus, recognizes host proteins in some species of animals, but we could not succeed in identifying the proteins. In the present study, we found that S16 cross-reacted with acetyl-CoA acyltransferase 2 (ACAA2), which is expressed in the livers of BALB/c mice. ACAA2 was released into the serum after acetaminophen (APAP) administration, and its serum level correlated with serum alanine aminotransferase (ALT) activity. Furthermore, we observed that S16 injected into mice with APAP-induced hepatic injury prompted the formation of an immune complex between S16 and ACAA2 in the serum. The levels of serum ALT (p < 0.01) and necrotic areas in the liver (p < 0.01) were reduced in the S16-injected mice. These results suggest that S16 may have a mitigation function in response to APAP-induced hepatotoxicity. This study shows the therapeutic function of an autoantibody and suggests that an antibody against extracellular ACAA2 might be a candidate for treating APAP-induced hepatic injury.

| S-EPMC8175586 | biostudies-literature

Transgenic expression of entire hepatitis B virus in mice induces hepatocarcinogenesis independent of chronic liver injury.

Project description:Hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide, is most commonly caused by chronic hepatitis B virus (HBV) infection. However, whether HBV plays any direct role in carcinogenesis, other than indirectly causing chronic liver injury by inciting the host immune response, remains unclear. We have established two independent transgenic mouse lines expressing the complete genome of a mutant HBV ("preS2 mutant") that is found at much higher frequencies in people with HCC than those without. The transgenic mice show evidence of stress in the endoplasmic reticulum (ER) and overexpression of cyclin D1 in hepatocytes. These mice do not show any evidence of chronic liver injury, but by 2 years of age a majority of the male mice develop hepatocellular neoplasms, including HCC. Unexpectedly, we also found a significant increase in hepatocarcinogenesis independent of necroinflammation in a transgenic line expressing the entire wildtype HBV. As in the mutant HBV mice, HCC was found only in aged--2-year-old--mice of the wildtype HBV line. The karyotype in all the three transgenic lines appears normal and none of the integration sites of the HBV transgene in the mice is near an oncogene or tumor suppressor gene. The significant increase of HCC incidence in all the three transgenic lines--expressing either mutant or wildtype HBV--therefore argues strongly that in absence of chronic necroinflammation, HBV can contribute directly to the development of HCC.

| S-EPMC3192172 | biostudies-literature

Subclinical brain injury caused by H5N1 influenza virus infection.

Project description:Although H5N1 influenza A viruses can cause systemic infection, their neurotropism and long-term effects on the central nervous system (CNS) are not fully understood. We assessed H5N1viral invasion of the CNS and its long-term effects in a ferret model. An H5N1 virus caused nonsuppurative encephalitis, which lasted for 3 months without neurologic signs. Further, another H5N1 virus caused nonsuppurative vasculitis with brain hemorrhage. Three-dimensional analysis of viral distribution in the brain identified the olfactory system as a major route for brain invasion. The efficient growth of virus in the upper respiratory tract may thus facilitate viral brain invasion.

| S-EPMC3126180 | biostudies-literature

Influenza virus infection induces widespread alterations of host cell splicing

Project description:Influenza A viruses (IAV) use diverse mechanisms to interfere with cellular gene expression and thus limit the antiviral responses and/or promote viral replication. Although many RNAseq studies have documented IAV-induced changes in host mRNA abundance, few were designed to allow an accurate quantification of changes in host mRNA splicing. Here we show that IAV infection of human lung cells induces widespread alterations of cellular splicing, with an overall increase in exon inclusion and decrease in intron retention. Over half of the mRNAs that show differential splicing undergo no significant changes in abundance or in their 3’ end termination site, suggesting that IAV can directly manipulate cellular splicing independently of other transcriptional changes. Cross-analysis of the alternative splicing profiles of IAV-infected and RED-depleted cells demonstrates a partial phenocopying of the RED-knock down phenotype in infected cells, suggesting that hijacking of the RED factor by IAVs to promote splicing of their own mRNAs could account for a minor subset of splicing changes in infected cells. All our results can be expored through a Shiny user friendly interface (http://virhostnet.prabi.fr:3838/shinyapps/flu-splicing).

2020-08-31 | GSE154596 | GEO

Influenza virus infection induces widespread alterations of host cell splicing.

Project description:Influenza A viruses (IAVs) use diverse mechanisms to interfere with cellular gene expression. Although many RNA-seq studies have documented IAV-induced changes in host mRNA abundance, few were designed to allow an accurate quantification of changes in host mRNA splicing. Here, we show that IAV infection of human lung cells induces widespread alterations of cellular splicing, with an overall increase in exon inclusion and decrease in intron retention. Over half of the mRNAs that show differential splicing undergo no significant changes in abundance or in their 3' end termination site, suggesting that IAVs can specifically manipulate cellular splicing. Among a randomly selected subset of 21 IAV-sensitive alternative splicing events, most are specific to IAV infection as they are not observed upon infection with VSV, induction of interferon expression or induction of an osmotic stress. Finally, the analysis of splicing changes in RED-depleted cells reveals a limited but significant overlap with the splicing changes in IAV-infected cells. This observation suggests that hijacking of RED by IAVs to promote splicing of the abundant viral NS1 mRNAs could partially divert RED from its target mRNAs. All our RNA-seq datasets and analyses are made accessible for browsing through a user-friendly Shiny interface (http://virhostnet.prabi.fr:3838/shinyapps/flu-splicing or https://github.com/cbenoitp/flu-splicing).

| S-EPMC7680258 | biostudies-literature

IL-6 ameliorates acute lung injury in influenza virus infection.

Project description:Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens. It also participates in the process of influenza infection by affecting viral clearance and immune cell responses. However, whether IL-6 impacts lung repair in influenza pathogenesis remains unclear. Here, we studied the role of IL-6 in acute influenza infection in mice. IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts. Deficiency in IL-6 enhanced proliferation, migration and survival of lung fibroblasts, as well as increased virus-induced apoptosis of lung epithelial cells. IL-6-deficient lung fibroblasts produced elevated levels of TGF-β, which may contribute to their survival. Furthermore, macrophage recruitment to the lung and phagocytic activities of macrophages during influenza infection were reduced in IL-6-deficient mice. Collectively, our results indicate that IL-6 is crucial for lung repair after influenza-induced lung injury through reducing fibroblast accumulation, promoting epithelial cell survival, increasing macrophage recruitment to the lung and enhancing phagocytosis of viruses by macrophages. This study suggests that IL-6 may be exploited for lung repair during influenza infection.

| S-EPMC5338329 | biostudies-literature

Influenza A Virus (H1N1) Infection Induces Glycolysis to Facilitate Viral Replication.

Project description:Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus (H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial (A549) cells. In detail, the expression of hexokinase 2 (HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells, and the expression of pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase kinase 3 (PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1 (HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.

| S-EPMC8692537 | biostudies-literature

Adeno-Associated Virus Vector Mediated Delivery of the HBV Genome Induces Chronic Hepatitis B Virus Infection and Liver Fibrosis in Mice.

Project description:Liver cirrhosis and hepatocellular carcinomas are major health problems of chronic hepatitis B virus (HBV) infection. To date, rare model has reproduced liver fibrosis associated with long-term HBV infection which in turn has hindered both the understanding of HBV biology and the development of new treatment options. Here, using adeno-associated virus serotype 8 (AAV8) mediated delivery of a 1.2-kb HBV genome, we successfully generated a chronic HBV infectious mouse model that presents the associated liver fibrosis observed following human infection. After AAV8/HBV1.2 vector administration, mice demonstrated effective HBV replication and transcription which resulted in HBV antigen expression and viremia over 6 months. Although no obvious acute inflammatory response was noted, these mice still developed chronic liver disease and hepatic fibrogenesis as demonstrated by increased ground glass-like hepatocytes, an increasing trend of collagen deposition and upregulated fibrosis markers, including type I collagen, type III collagen, tissue inhibitor of metalloproteinase (TIMP), and transforming growth factor-?1(TGF-?1). Taken together, AAV-mediated HBV gene delivery to the mouse liver, induced HBV persistent infection accompanied by liver fibrosis which can serve as a model for investigating the precise mechanisms underlying liver fibrosis following chronic HBV infection as well as for the potential development of novel therapeutics.

| S-EPMC4468063 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data