Hepatocytes that express variants of cyclophilin A are resistant to HCV infection and replication.

Abstract:

BACKGROUND & AIMS:Hepatitis C virus (HCV) uses several host factors to infect and replicate in human hepatocytes. Cyclophilin A (CypA) is required for viral replication, and CypA inhibitors are in development. We investigated the effects of nonsynonymous single nucleotide polymorphisms (SNPs) in the region of peptidyl-prolyl isomerase A (PPIA) that encodes CypA on HCV infection and replication of human hepatocytes. METHODS:We used a combination of virologic, biochemical, and genetic approaches to investigate the effects of PPIA variants on HCV replication in cultured Huh-7.5 cells. We reduced levels of CypA in these cells using small hairpin RNAs (shRNAs). RESULTS:Using shRNAs, we showed that CypA was required for replication of HCV in Huh-7.5 cells and identified 3 SNPs in PPIA that protected cells from HCV entry or replication. Levels of HCV RNA were reduced 3-4 log in cells homozygous for the variant alleles; release of new particles was also reduced, but viral entry was not affected. The effects of the variant alleles were recessive and stronger for preventing replication of full-length HCV genomes than subgenomes. CypA inhibitors prevented replication of residual HCV in hepatocytes. The variants appeared to destabilize the CypA protein; the single amino acid changes led to rapid degradation of the protein. CONCLUSIONS:We identified variants in PPIA that destabilize its product, CypA, and prevent HCV infection and replication. These findings indicate mechanisms by which some cells might be resistant to HCV infection and that CypA is a good therapeutic target.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

von Hahn T,Schiene-Fischer C,Van ND,Pfaender S,Karavul B,Steinmann E,Potthoff A,Strassburg C,Hamdi N,Abdelaziz AI,Sarrazin C,Müller T,Berg T,Trépo E,Wedemeyer H,Manns MP,Pietschmann T,Ciesek S

doi

10.1053/j.gastro.2012.04.053

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

439-47.e1

issue

2

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(12)00680-4

journal_volume

143

pub_type

杂志文章
  • Role of acquired and hereditary thrombotic risk factors in colon ischemia of ambulatory patients.

    abstract:BACKGROUND & AIMS:Hypercoagulable states may play an important role in the pathogenesis of colon ischemia. Aim of this study was to assess this hypothesis investigating the role of acquired and hereditary thrombotic risk factors in patients with definite diagnosis of colon ischemia. METHODS:We compared the frequency o...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2001.27227

    authors: Koutroubakis IE,Sfiridaki A,Theodoropoulou A,Kouroumalis EA

    更新日期:2001-09-01 00:00:00

  • Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat.

    abstract:BACKGROUND/AIMS:Gastrointestinal peptides and biogenic monoamines participate in the regulation of gastrointestinal functions. The aim of this study was to examine the influence of the microflora on the distribution of endocrine cells and on the release of gastrointestinal peptides. METHODS:A quantitative morphologica...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(94)90526-6

    authors: Uribe A,Alam M,Johansson O,Midtvedt T,Theodorsson E

    更新日期:1994-11-01 00:00:00

  • Fiberoptic endoscopy during laparotomy in the diagnosis of small intestinal bleeding.

    abstract::A patient with recurrent gastrointestinal bleeding caused by hereditary hemorrhagic telangiectasia localized to the small intestine is described. The diagnosis was made by combining two recognized investigational tools-fiberoptic endoscopy and laparotomy. ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Greenberg GR,Phillips MJ,Tovee EB,Jeejeebhoy KN

    更新日期:1976-07-01 00:00:00

  • Antroduodenal resistance to flow in the control of duodenogastric bile reflux during fasting.

    abstract::Our objectives in this study were (a) to determine the role of antroduodenal resistance in the control of fasting duodenogastric bile reflux in the dog and (b) to elucidate the contribution of the pylorus both to resistance and to reflux. Thus, we measured simultaneously throughout the interdigestive motor cycle (a) a...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(87)90566-x

    authors: Mearin F,Azpiroz F,Malagelada JR,Zinsmeister AR

    更新日期:1987-11-01 00:00:00

  • Bile-salt metabolism in the primate fetus.

    abstract::Fetal bile salt metabolism was assessed by the intravenous infusion of e114C]cholate into 6 monkey fetuses. The placental transfer, fetal plasma clearance, and fetal hepatic excretion of the administered radiolabeled bile salt were measured. Placental transfer averaged 30% of the injected dose, while biliary excretion...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Little JM,Smallwood RA,Lester R,Piasecki GJ,Jackson BT

    更新日期:1975-12-01 00:00:00

  • Somatosensory evoked potentials in hepatic encephalopathy.

    abstract::Median nerve somatosensory evoked potentials were recorded from 33 patients with various degrees of hepatic failure and from 10 age-matched controls. Within 20 ms poststimulation, one negative peak (N13) could be recorded from the middle of the back of the patient's neck at the C2 vertebral level. Within 150 ms, three...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(85)90460-3

    authors: Yang SS,Chu NS,Liaw YF

    更新日期:1985-09-01 00:00:00

  • Heterogeneities in ICC Ca2+ activity within canine large intestine.

    abstract:BACKGROUND & AIMS:In human and canine colon, both slow (slow waves, 2-8/min) and fast (myenteric potential oscillations [MPOs]; 16-20/min) electrical rhythms in the smooth muscle originate at the submucosal and myenteric borders, respectively. We used Ca(2+) imaging to investigate whether interstitial cells of Cajal (I...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2009.02.060

    authors: Lee HT,Hennig GW,Park KJ,Bayguinov PO,Ward SM,Sanders KM,Smith TK

    更新日期:2009-06-01 00:00:00

  • Ultrasound-Mediated Delivery of RNA to Colonic Mucosa of Live Mice.

    abstract:BACKGROUND & AIMS:It is a challenge to deliver nucleic acids to gastrointestinal (GI) tissues due to their size and need for intracellular delivery. They are also extremely susceptible to degradation by nucleases, which are ubiquitous in the GI tract. We investigated whether ultrasound, which can permeabilize tissue th...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2017.01.002

    authors: Schoellhammer CM,Lauwers GY,Goettel JA,Oberli MA,Cleveland C,Park JY,Minahan D,Chen Y,Anderson DG,Jaklenec A,Snapper SB,Langer R,Traverso G

    更新日期:2017-04-01 00:00:00

  • Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C.

    abstract:BACKGROUND & AIMS:Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 ...

    journal_title:Gastroenterology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1053/j.gastro.2011.03.010

    authors: Bruix J,Poynard T,Colombo M,Schiff E,Burak K,Heathcote EJ,Berg T,Poo JL,Mello CB,Guenther R,Niederau C,Terg R,Bedossa P,Boparai N,Griffel LH,Burroughs M,Brass CA,Albrecht JK,EPIC3 Study Group.

    更新日期:2011-06-01 00:00:00

  • Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa.

    abstract:BACKGROUND & AIMS:Therapy with interferon alfa (IFN-alpha) leads to remission of disease in one third of patients with chronic hepatitis B. The aim of this study was to better define the long-term prognosis of this outcome. METHODS:One hundred three patients with chronic hepatitis B who underwent IFN-alpha therapy in ...

    journal_title:Gastroenterology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1053/gast.1997.v113.pm9352870

    authors: Lau DT,Everhart J,Kleiner DE,Park Y,Vergalla J,Schmid P,Hoofnagle JH

    更新日期:1997-11-01 00:00:00

  • Ritanserin decreases portal pressure in conscious and unrestrained cirrhotic rats.

    abstract::We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and syst...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(90)91302-m

    authors: Mastai R,Giroux L,Semret M,Huet PM

    更新日期:1990-01-01 00:00:00

  • Genetic variants in cyclooxygenase-2: Expression and risk of gastric cancer and its precursors in a Chinese population.

    abstract:BACKGROUND & AIMS:To screen the genetic variants in cyclooxygenase-2 (COX-2), and evaluate their effects on COX-2 expression and risk of gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, Shangdong Province, an area of China, a high-risk area of GC. METHODS:Genotypes were d...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2006.03.021

    authors: Liu F,Pan K,Zhang X,Zhang Y,Zhang L,Ma J,Dong C,Shen L,Li J,Deng D,Lin D,You W

    更新日期:2006-06-01 00:00:00

  • Delayed enzyme expression: a defect of aging rat gut.

    abstract::To evaluate the effect of aging upon the small intestine, the distribution, content, and concentration of epithelial cell enzymes at different levels along the crypt-villus column were measured in aging and young adult, male, Fisher 344 rats. Specific activities of sucrase, maltase, lactase, and adenosine deaminase in...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(85)90204-5

    authors: Holt PR,Tierney AR,Kotler DP

    更新日期:1985-11-01 00:00:00

  • Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia.

    abstract::Endoscopic screening in 123 patients with pernicious anemia (PA) yielded 4 patients with solitary and 1 patient with multiple gastric carcinoid tumors. Quantitative histologic studies of multiple standardized biopsy specimens showed a significantly increased number of fundic mucosal argyrophil endocrine cells in 40 pa...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(85)90131-3

    authors: Borch K,Renvall H,Liedberg G

    更新日期:1985-03-01 00:00:00

  • Bioavailability of cimetidine in man.

    abstract::The bioavailability of parenteral cimetidine was tested in 12 volunteers in a balanced three-way crossover study. Blood levels and urinary excretion were compared after intramuscular and intravenous injection and oral administration of 300 mg of cinetidine. The results indicated that the intramuscular and intravenous ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Walkenstein SS,Dubb JW,Randolph WC,Westlake WJ,Stote RM,Intoccia AP

    更新日期:1978-02-01 00:00:00

  • The many faces of celiac disease: clinical presentation of celiac disease in the adult population.

    abstract::The major modes of presentation of patients with celiac disease are the classic diarrhea-predominant form and silent celiac disease. Those with silent celiac disease lack diarrhea, although they may present with manifestations of celiac disease that include an irritable bowel syndrome, anemia, osteoporosis, neurologic...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2005.02.016

    authors: Green PH

    更新日期:2005-04-01 00:00:00

  • Once-daily, high-concentration MMX mesalamine in active ulcerative colitis.

    abstract:BACKGROUND & AIMS:SPD476 (LIALDA in the US; MEZAVANT in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology desi...

    journal_title:Gastroenterology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1053/j.gastro.2006.10.011

    authors: Kamm MA,Sandborn WJ,Gassull M,Schreiber S,Jackowski L,Butler T,Lyne A,Stephenson D,Palmen M,Joseph RE

    更新日期:2007-01-01 00:00:00

  • Ingestion of corrosive acids. Spectrum of injury to upper gastrointestinal tract and natural history.

    abstract::We have prospectively evaluated 41 patients who ingested acid for location, extent, severity, and outcome of the injury to the upper gastrointestinal tract. The injury was assessed within 36 h of acid intake by endoscopy or surgery, or at autopsy. Symptoms and signs were unreliable in predicting the extent and severit...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Zargar SA,Kochhar R,Nagi B,Mehta S,Mehta SK

    更新日期:1989-09-01 00:00:00

  • Prospective identification of a multilineage progenitor in murine stomach epithelium.

    abstract:BACKGROUND & AIMS:Epithelial stem cells in the stomach are responsible for constant renewal of the epithelium through generation of multiple gastric cell lineages that populate the gastric glands. However, gastric stem or progenitor cells have not been well-characterized because of the lack of specific markers that per...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2007.09.031

    authors: Qiao XT,Ziel JW,McKimpson W,Madison BB,Todisco A,Merchant JL,Samuelson LC,Gumucio DL

    更新日期:2007-12-01 00:00:00

  • Communication via gap junctions modulates bile secretion in the isolated perfused rat liver.

    abstract:BACKGROUND & AIMS:Bile secretion is regulated in part by adenosine 3',5'-cyclic monophosphate (cAMP) and cytosolic Ca2+ (Ca2+i). Hormone receptors that link to these second messengers are not uniformly distributed across the hepatic lobule, but both cAMP and Ca2+i cross gap junctions, so we tested whether gap junctiona...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(99)70021-1

    authors: Nathanson MH,Rios-Velez L,Burgstahler AD,Mennone A

    更新日期:1999-05-01 00:00:00

  • Distribution of somatostatin-14 and somatostatin-28 gastrointestinal-pancreatic cells of rats and humans.

    abstract::Somatostatin-14 and somatostatin-28 are biologically active peptides derived from the posttranslational cleavage of prosomatostatin. Because both peptides are found in variable concentrations in the gastrointestinal (GI) tract and pancreas, it has been contended that somatostatin-28 is either an intermediate in the pr...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(90)91151-u

    authors: Francis BH,Baskin DG,Saunders DR,Ensinck JW

    更新日期:1990-11-01 00:00:00

  • Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function.

    abstract:BACKGROUND & AIMS:Hirschsprung disease is caused by failure of enteric neural crest cells (ENCCs) to fully colonize the bowel, leading to bowel obstruction and megacolon. Heterozygous mutations in the coding region of the RET gene cause a severe form of Hirschsprung disease (total colonic aganglionosis). However, 80% o...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2017.03.014

    authors: Lai FP,Lau ST,Wong JK,Gui H,Wang RX,Zhou T,Lai WH,Tse HF,Tam PK,Garcia-Barcelo MM,Ngan ES

    更新日期:2017-07-01 00:00:00

  • Early detection of protein depletion in alcoholic cirrhosis: role of body composition analysis.

    abstract:BACKGROUND:Malnutrition is common in alcoholic cirrhosis. Bedside nutritional assessment techniques may be unreliable in patients with chronic liver disease. The aim of this study was to quantify changes in body composition and compare methods for measuring body composition in alcoholic cirrhosis. METHODS:Thirty-eight...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(93)91083-t

    authors: Prijatmoko D,Strauss BJ,Lambert JR,Sievert W,Stroud DB,Wahlqvist ML,Katz B,Colman J,Jones P,Korman MG

    更新日期:1993-12-01 00:00:00

  • Orthotopic liver transplantation for graft-versus-host disease following bone marrow transplantation.

    abstract::Chronic graft-vs.-host disease occurs in 30%-50% of long-term survivors of allogeneic bone marrow grafts, and may eventuate in cirrhosis. In this study, a young woman, originally diagnosed as having acute myelogenous leukemia, underwent successful bone marrow transplantation but later developed graft-vs.-host disease-...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(90)91039-9

    authors: Rhodes DF,Lee WM,Wingard JR,Pavy MD,Santos GW,Shaw BW,Wood RP,Sorrell MF,Markin RS

    更新日期:1990-08-01 00:00:00

  • Circulating levels of endothelin in cirrhosis.

    abstract:BACKGROUND:Current information concerning endothelin in cirrhosis is conflicting. Plasma endothelin concentration has been found to be increased in some studies and normal or reduced in others. The present study was aimed to investigate the plasma levels of endothelin in cirrhosis and to assess whether it is involved i...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(93)90360-o

    authors: Asbert M,Ginès A,Ginès P,Jiménez W,Clària J,Saló J,Arroyo V,Rivera F,Rodés J

    更新日期:1993-05-01 00:00:00

  • Prokinetic effects in patients with intestinal gas retention.

    abstract:BACKGROUND & AIMS:We have previously shown that patients with irritable bowel syndrome (IBS) have impaired transit of intestinal gas loads. Because abnormal gas retention can be experimentally reproduced in healthy subjects by pharmacological inhibition of gut motility, we hypothesized that impaired gas transit and ret...

    journal_title:Gastroenterology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1053/gast.2002.33658

    authors: Caldarella MP,Serra J,Azpiroz F,Malagelada JR

    更新日期:2002-06-01 00:00:00

  • Ornithine decarboxylase activity in Barrett's esophagus: a potential marker for dysplasia.

    abstract::Ornithine decarboxylase activity is known to be increased in certain premalignant conditions. We determined the activity of this enzyme in mucosal biopsy specimens from 15 patients with Barrett's esophagus. Ornithine decarboxylase was greater in Barrett's mucosa than in squamous esophageal or gastric mucosa. In Barret...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(88)90259-4

    authors: Garewal HS,Sampliner R,Gerner E,Steinbronn K,Alberts D,Kendall D

    更新日期:1988-03-01 00:00:00

  • Effect of institution-wide policy of colonoscopy withdrawal time > or = 7 minutes on polyp detection.

    abstract:BACKGROUND & AIMS:Practice guidelines recommend that endoscopists spend at least 7 minutes examining the colonic mucosa during colonoscopy withdrawal to optimize polyp yield. The aim of this study was to determine if the implementation of an institution-wide policy of colonoscopy withdrawal time > or = 7 minutes was as...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2008.08.024

    authors: Sawhney MS,Cury MS,Neeman N,Ngo LH,Lewis JM,Chuttani R,Pleskow DK,Aronson MD

    更新日期:2008-12-01 00:00:00

  • Interdigestive phasic contractions of the human lower esophageal sphincter.

    abstract::The results of this study show that lower esophageal sphincter contractions occur during phases 2 and 3 of the gastric interdigestive migratory motor complex in humans. In one series of studies, esophageal, gastric, and duodenal pressures were monitored overnight for 12 h in 7 healthy, fasting subjects. A second group...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Dent J,Dodds WJ,Sekiguchi T,Hogan WJ,Arndorfer RC

    更新日期:1983-03-01 00:00:00

  • CD39/ENTPD1 expression by CD4+Foxp3+ regulatory T cells promotes hepatic metastatic tumor growth in mice.

    abstract:BACKGROUND & AIMS:Adenosine mediates immune suppression and is generated by the ectonucleotidases CD39 (ENTPD1) and CD73 that are expressed on vascular endothelial cells and regulatory T cells (Tregs). Although tumor-infiltrating immune cells include Foxp3(+) Tregs, it is not clear whether local adenosine generation by...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2010.05.007

    authors: Sun X,Wu Y,Gao W,Enjyoji K,Csizmadia E,Müller CE,Murakami T,Robson SC

    更新日期:2010-09-01 00:00:00