scholarly journals Hepatitis C Virus p7 Induces Membrane Permeabilization by Interacting with Phosphatidylserine

2020 ◽  
Vol 21 (3) ◽  
pp. 897
Author(s):  
Hye-Ra Lee ◽  
Gi Young Lee ◽  
Deok-Gyun You ◽  
Hong Kyu Kim ◽  
Young Do Yoo
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Essential Role ◽  
Molecular Target ◽  
Membrane Permeabilization ◽  
Endoplasmic Reticulum Membrane ◽  
Nonselective Cation Channel ◽  
Channel Activity ◽  
Mitochondrial Depolarization ◽  
Hcv Therapy

Hepatitis C virus (HCV) p7 is known to be a nonselective cation channel for HCV maturation. Because the interaction of HCV proteins with host lipids in the endoplasmic reticulum membrane is crucial for the budding process, the identification of p7–lipid interactions could be important for understanding the HCV life cycle. Here, we report that p7 interacts with phosphatidylserine (PS) to induce membrane permeabilization. The interaction of p7 with PS was not inhibited by Gd3+ ions, which have been known to interact with negatively charged lipids, but channel activity and p7-induced mitochondrial depolarization were inhibited by Gd3+ ions. From the present results, we suggest that the p7–PS interaction plays an essential role in regulating its ion channel function and could be a potential molecular target for anti-HCV therapy.

scholarly journals Diffuse Alveolar Hemorrhage (DAH) in Hepatitis C Virus (HCV) Associated Cryoglobulinemia After Completion of HCV Therapy

CHEST Journal ◽  
2016 ◽  
Vol 150 (4) ◽  
pp. 530A
Author(s):  
Abhijai Singh ◽  
Chandrakanta Chuturvedula ◽  
Gurbir GIll ◽  
Reshma Abraham ◽  
Pieusha Malhotra
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Hcv Therapy

scholarly journals Evaluation of Oral Cannabinoid-Containing Medications for the Management of Interferon and Ribavirin-Induced Anorexia, Nausea and Weight Loss in Patients Treated for Chronic Hepatitis C Virus

2008 ◽  
Vol 22 (4) ◽  
pp. 376-380 ◽  
Author(s):  
Cecilia T Costiniuk ◽  
Edward Mills ◽  
Curtis L Cooper
Keyword(s):  
Weight Loss ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Side Effects ◽  
Cohort Analysis ◽  
Smoking History ◽  
Hcv Treatment ◽  
Hcv Therapy ◽  
Median Weight Loss ◽  
Dose Reductions

OBJECTIVES: The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown.METHODS: All patients who initiated interferon-ribavirin therapy at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between August 2003 and January 2007 were identified using a computerized clinical database. The baseline characteristics of OC recipients were compared with those of nonrecipients. The treatment-related side effect response to OC was assessed by χ2analysis. The key therapeutic outcomes related to weight, interferon dose reduction and treatment outcomes were assessed by Student’sttest and χ2analysis.RESULTS: Twenty-five of 191 patients (13%) initiated OC use. Recipients had similar characteristics to nonrecipients, aside from prior marijuana smoking history (24% versus 10%, respectively; P=0.04). The median time to OC initiation was seven weeks. The most common indications for initiation of OC were anorexia (72%) and nausea (32%). Sixty-four per cent of all patients who received OC experienced subjective improvement in symptoms. The median weight loss before OC initiation was 4.5 kg. A trend toward greater median weight loss was noted at week 4 in patients eventually initiating OC use (−1.4 kg), compared with those who did not (−1.0 kg). Weight loss stabilized one month after OC initiation (median 0.5 kg additional loss). Interferon dose reductions were rare and did not differ by OC use (8% of OC recipients versus 5% of nonrecipients). The proportions of patients completing a full course of HCV therapy and achieving a sustained virological response were greater in OC recipients.CONCLUSIONS: The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.

scholarly journals The Tight Junction-Associated Protein Occludin Is Required for a Postbinding Step in Hepatitis C Virus Entry and Infection

2009 ◽  
Vol 83 (16) ◽  
pp. 8012-8020 ◽  
Author(s):  
Ignacio Benedicto ◽  
Francisca Molina-Jiménez ◽  
Birke Bartosch ◽  
François-Loïc Cosset ◽  
Dimitri Lavillette ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Surface ◽  
Tight Junction ◽  
Essential Role ◽  
Surface Protein ◽  
Hcv Infection ◽  
Surface Proteins ◽  
Target Cells ◽  
Type I

ABSTRACT The precise mechanisms regulating hepatitis C virus (HCV) entry into hepatic cells remain unknown. However, several cell surface proteins have been identified as entry factors for this virus. Of these molecules, claudin-1, a tight junction (TJ) component, is considered a coreceptor required for HCV entry. Recently, we have demonstrated that HCV envelope glycoproteins (HCVgp) promote structural and functional TJ alterations. Additionally, we have shown that the intracellular interaction between viral E2 glycoprotein and occludin, another TJ-associated protein, could be the cause of the mislocalization of TJ proteins. Herein we demonstrated, by using cell culture-derived HCV particles (HCVcc), that interference of occludin expression markedly reduced HCV infection. Furthermore, our results with HCV pseudotyped particles indicated that occludin, but not other TJ-associated proteins, such as junctional adhesion molecule A or zonula occludens protein 1, was required for HCV entry. Using HCVcc, we demonstrated that occludin did not play an essential role in the initial attachment of HCV to target cells. Surface protein labeling experiments showed that both expression levels and cell surface localization of HCV (co)receptors CD81, scavenger receptor class B type I, and claudin-1 were not affected upon occludin knockdown. In addition, immunofluorescence confocal analysis showed that occludin interference did not affect subcellular distribution of the HCV (co)receptors analyzed. However, HCVgp fusion-associated events were altered after occludin silencing. In summary, we propose that occludin plays an essential role in HCV infection and probably affects late entry events. This observation may provide new insights into HCV infection and related pathogenesis.

scholarly journals A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria

2004 ◽  
Vol 85 (2) ◽  
pp. 451-461 ◽  
Author(s):  
Stephen D. C. Griffin ◽  
Ruth Harvey ◽  
Dean S. Clarke ◽  
Wendy S. Barclay ◽  
Mark Harris ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Ion Channel ◽  
Lipid Bilayers ◽  
Mammalian Cells ◽  
Intracellular Localization ◽  
Channel Activity ◽  
Diarrhoea Virus ◽  
Basic Loop

We previously identified the function of the hepatitis C virus (HCV) p7 protein as an ion channel in artificial lipid bilayers and demonstrated that this in vitro activity is inhibited by amantadine. Here we show that the ion channel activity of HCV p7 expressed in mammalian cells can substitute for that of influenza virus M2 in a cell-based assay. This was also the case for the p7 from the related virus, bovine viral diarrhoea virus (BVDV). Moreover, amantadine was shown to abrogate HCV p7 function in this assay at a concentration that specifically inhibits M2. Mutation of a conserved basic loop located between the two predicted trans-membrane alpha helices rendered HCV p7 non-functional as an ion channel. The intracellular localization of p7 was unaffected by this mutation and was found to overlap significantly with membranes associated with mitochondria. Demonstration of p7 ion channel activity in cellular membranes and its inhibition by amantadine affirm the protein as a target for future anti-viral chemotherapy.

scholarly journals Hepatitis C virus (HCV) associated steatosis and increased gluconeogenic gene expression in Huh8 cells: essential role of NS5A and C/EBPâ

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Mahua Choudhury ◽  
Ishtiaq Qadri ◽  
Mizanoor Rahman ◽  
Trina a Knotts ◽  
Rachel c Janssen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Essential Role
Sign in / Sign up

Export Citation Format

Share Document