MicroRNA 130a Regulates both Hepatitis C Virus and Hepatitis B Virus Replication through a Central Metabolic Pathway

ABSTRACTHepatitis C virus (HCV) infection has been shown to regulate microRNA 130a (miR-130a) in patient biopsy specimens and in cultured cells. We sought to identify miR-130a target genes and to explore the mechanisms by which miR-130a regulates HCV and hepatitis B virus (HBV) replication. We used bioinformatics software, including miRanda, TargetScan, PITA, and RNAhybrid, to predict potential miR-130a target genes. miR-130a and its target genes were overexpressed or were knocked down by use of small interfering RNA (siRNA) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 guide RNA (gRNA). Selected gene mRNAs and their proteins, together with HCV replication in OR6 cells, HCV JFH1-infected Huh7.5.1 cells, and HCV JFH1-infected primary human hepatocytes (PHHs) and HBV replication in HepAD38 cells, HBV-infected NTCP-Huh7.5.1 cells, and HBV-infected PHHs, were measured by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting, respectively. We selected 116 predicted target genes whose expression was related to viral pathogenesis or immunity for qPCR validation. Of these, the gene encoding pyruvate kinase in liver and red blood cell (PKLR) was confirmed to be regulated by miR-130a overexpression. miR-130a overexpression (via a mimic) knocked down PKLR mRNA and protein levels. A miR-130a inhibitor and gRNA increased PKLR expression, HCV replication, and HBV replication, while miR-130a gRNA and PKLR overexpression increased HCV and HBV replication. Supplemental pyruvate increased HCV and HBV replication and rescued the inhibition of HCV and HBV replication by the miR-130a mimic and PKLR knockdown. We concluded that miR-130a regulates HCV and HBV replication through its targeting of PKLR and subsequent pyruvate production. Our data provide novel insights into key metabolic enzymatic pathway steps regulated by miR-130a, including the steps involving PKLR and pyruvate, which are subverted by HCV and HBV replication.IMPORTANCEWe identified that miR-130a regulates the target genePKLRand its subsequent effect on pyruvate production. Pyruvate is a key intermediate in several metabolic pathways, and we identified that pyruvate plays a key role in regulation of HCV and HBV replication. This previously unrecognized, miRNA-regulated antiviral mechanism has implications for the development of host-directed strategies to interrupt the viral life cycle and prevent establishment of persistent infection for HCV, HBV, and potentially other viral infections.

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Hepatitis C virus core protein inhibits hepatitis B virus replication by downregulating HBx levels via Siah-1-mediated proteasomal degradation during coinfection

Journal of General Virology ◽

10.1099/jgv.0.001701 ◽

2021 ◽

Vol 102 (12) ◽

Author(s):

Sujeong Lee ◽

Hyunyoung Yoon ◽

Jiwoo Han ◽

Kyung Lib Jang

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Core Protein ◽

Experimental Studies ◽

Proteasomal Degradation ◽

Hbv Replication ◽

Hcv Core Protein ◽

B Virus

Most clinical and experimental studies have suggested that hepatitis C virus (HCV) is dominant over hepatitis B virus (HBV) during coinfection, although the mechanism remains unclear. Here, we found that HCV core protein inhibits HBV replication by downregulating HBx levels during coinfection in human hepatoma cells. For this effect, HCV core protein increased reactive oxygen species levels in the mitochondria and activated the ataxia telangiectasia mutated-checkpoint kinase two pathway in the nucleus, resulting in an upregulation of p53 levels. Accordingly, HCV core protein induced p53-dependent activation of seven in absentia homolog one expression, an E3 ligase of HBx, resulting in the ubiquitination and proteasomal degradation of HBx. The effect of the HCV core protein on HBx levels was accurately reproduced in both a 1.2-mer HBV replicon and in vitro HBV infection systems, providing evidence for the inhibition of HBV replication by HCV core protein. The present study may provide insights into the mechanism of HCV dominance in HBV- and HCV-coinfected patients.

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ACREDITED MOLECULAR METHODS FOR DETECTION OF INFECTIONS CAUSED BY HIV, HEPATITIS B VIRUS AND HEPATITIS C VIRUS

Knowledge International Journal ◽

10.35120/kij3104917g ◽

2019 ◽

Vol 31 (4) ◽

pp. 917-920

Author(s):

Belinda Gelmanovska ◽

Vaso Taleski

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Infectious Diseases ◽

Molecular Diagnostics ◽

Viral Infections ◽

Molecular Methods ◽

Great Success ◽

B Virus

Hepatitis B and C, as well as HIV infections are common pathology in present time. According current assessments 350 million are carriers of Hepatitis B virus, 170 million of Hepatitis C virus and over 60 million infected by HIV. Timely detection and prompt diagnosis of these viral infections are of great importance. According assessments, in our country about 1 of 50 persons are infected by Hepatitis B or Hepatitis C. From the beginning of the epidemic in 1987, until 2016 total number of registered of HIV/AIDS is 311 (179 with AIDS and 131 HIV positive). In JZU - University Clinic for Infectious Diseases and Febrile Conditions Skopje, diagnosis of these viral infections are made by accredited molecular diagnostics methods, PCR, at Department for molecular diagnostics using HCV-RNA, HBV-DNA and HIV-RNA. Aims of accreditation of particular procedures in laboratories is protection and advancing of human health, and preventing of spreading of viral infections. With great success, Department for molecular diagnostics as part of the University Clinic For Infectious Diseases and Febrile Conditions Skopje use the System for quality management according standard MKS EN ISO 15189:2013 for medical laboratories. Accredited molecular methods in use for detection of Hepatitis C virus, Hepatitis B virus and HIV are Polymerase Chain Reaction (PCR) and Genotypisation of HCV with method of Reverse hybridization.

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Acute hepatitis C virus (HCV) infection in chronic carriers of hepatitis B virus (HBV): the impact of underlying active HBV replication on persistence of HCV infection and antibody responses to HCV

Gut ◽

10.1136/gut.51.1.95 ◽

2002 ◽

Vol 51 (1) ◽

pp. 95-99 ◽

Cited By ~ 21

Author(s):

C-M Chu ◽

C T Yeh ◽

I S Sheen ◽

Y F Liaw

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hcv Infection ◽

Antibody Responses ◽

Acute Hepatitis C ◽

Hbv Replication ◽

B Virus ◽

The Impact

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Prevalence of hepatitis B and C virus co-infection in HIV positive patients attending a health institution in southeast Nigeria

African Health Sciences ◽

10.4314/ahs.v20i2.5 ◽

2020 ◽

Vol 20 (2) ◽

pp. 579-586

Author(s):

Ifeyinwa Dorothy Nnakenyi ◽

Chisom Uchechukwu ◽

Uloaku Nto-ezimah

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Viral Infections ◽

Hepatitis B Surface Antigen ◽

Hiv Positive ◽

People Living With Hiv ◽

Number Of Patients ◽

B Virus

Background: The health of people living with HIV/AIDS becomes progressively worse when co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), resulting in shortened life span. The modes of transmission of HIV, HBV and HCV are similar. Objective: To determine the prevalence of HBV and HCV co-infection in HIV patients. Method: This was a retrospective study of serology test results for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) of HIV positive patients registered from 2008-2013 (6years) at the University of Nigeria Teaching Hospi- tal. Adult patients with confirmed HIV seropositivity were included. Ethical approval was obtained and confidentiality of the patient information was maintained. Laboratory records were reviewed to obtain HBsAg, anti-HCV, and CD4 T-lymphocyte results. Prevalence was determined by the number of positive results over total number of patients tested. Chi-square test was used to determine relationships and p<0.05 was considered to be statistically significant. Results: 4663 HIV patient records were included comprising 3024 (65%) females and 1639 (35%) males. Serology results showed 365/4663 (7.8%) tested HBsAg-positive only; 219/4663 (4.7%) tested anti-HCV-positive only; and 27/4663 (0.58%) tested both HBsAg and anti-HCV-positive. Correlation of age and sex were statistically significant with HBV and HCV (p<0.05) but not CD4 count (p>0.05). Conclusion: HBV co-infection was more prevalent than HCV, and triple infection was also observed. Screening for these viral infections in the HIV population is necessary for early identification to enable appropriate, holistic management of these patients. Keywords: Hepatitis B virus; Hepatitis C virus; HIV; co-infection.

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Alkoholabstinenz allein verbessert die Leberfunktion und verlängert das Überleben bei der alkoholischen Lebererkrankung!

SUCHT - Zeitschrift für Wissenschaft und Praxis / Journal of Addiction Research and Practice ◽

10.1024/0939-5911/a000459 ◽

2016 ◽

Vol 62 (6) ◽

pp. 396-400 ◽

Cited By ~ 1

Author(s):

Helmut K. Seitz ◽

Tatjana Arslic-Schmitt

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

B Virus ◽

Alkoholische Lebererkrankung ◽

Alkoholische Steatohepatitis

Zusammenfassung. Zielsetzung: Im Folgenden soll dargelegt werden, dass Alkoholkarenz sowohl die Leberfunktion als auch das Überleben in jedem Stadium einer alkoholischen Lebererkrankung günstig beeinflusst. Ergebnisse: Täglicher Alkoholkonsum von mehr als 25 Gramm reinen Alkohols, etwas mehr als ¼ Liter Wein beim Mann und etwa die Hälfte bei der Frau sind, mit einem erhöhten Risiko für eine alkoholische Lebererkrankung (ALE) behaftet. Die ALE besteht aus einem breiten Spektrum von histopathologischen Veränderungen. Sie beginnt immer mit einer alkoholischen Fettleber, die sich in eine alkoholische Steatohepatitis weiterentwickeln kann. Fortgeschrittene Formen der ALE beinhalten die Leberfibrose, die Leberzirrhose und das hepatozelluläre Karzinom. In der Behandlung jeder Form der ALE ist die Alkoholabstinenz von zentraler Bedeutung. Ein Großteil der alkoholischen Fettlebern bildet sich unter Alkoholkarenz oder sogar Alkoholreduktion zurück. Die alkoholische Hepatitis, ein klinisches Syndrom mit hoher Mortalität, führt ohne Alkoholkarenz innerhalb von Tagen und Wochen zum Tode. Darüber hinaus ist selbst die Leberfibrose (perivenös und perisinusoidal) unter Alkoholkarenz rückbildungsfähig. Bei allen Formen der fortgeschrittenen ALE (kompensiert und nicht-kompensierte Leberzirrhose) wird die Mortalität durch Alkoholkarenz oder signifikante Reduktion im Gegensatz zum fortgesetzten Alkoholkonsum signifikant verringert. Selbst Patienten mit alkoholischer Leberzirrhose können über mehr als 20 Jahre ohne Komplikationen weiterleben, wenn sie komplett auf Alkohol verzichten. Schlussfolgerung: Im Vergleich zu Leberzirrhose anderer Ätiologie, wie zum Beispiel Zirrhosen, die durch das Hepatitis-B Virus oder das Hepatitis-C Virus verursacht sind, haben alkoholische Leberzirrhosen unter Alkoholkarenz eine wesentlich bessere Prognose. Damit ist Alkoholkarenz eine gute Therapie und der Erfolg jeder anderen neuen Therapie muss mit Alkoholkarenz verglichen werden.

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Faculty Opinions recommendation of Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727423169.793545260 ◽

2018 ◽

Author(s):

Tilman Sauerbruch

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Population Based ◽

Population Based Study ◽

B Virus

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Disparities in Time to Treatment of Hepatocellular Carcinoma in Patients with Hepatitis B Virus versus Hepatitis C Virus

Archives in Cancer Research ◽

10.21767/2254-6081.100154 ◽

2017 ◽

Vol 05 (03) ◽

Author(s):

Jennifer Wu ◽

Tsivia Hochman ◽

Judith D Goldberg ◽

Jafar Al Mondhiry ◽

Bennal Perkins ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Time To Treatment ◽

B Virus ◽

Virus Versus

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Algorithms for the Testing of Tissue Donors for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus

Transfusion Medicine and Hemotherapy ◽

10.1159/000513179 ◽

2020 ◽

pp. 1-10

Author(s):

Axel Pruß ◽

Akila Chandrasekar ◽

Jacinto Sánchez-Ibáñez ◽

Sophie Lucas-Samuel ◽

Ulrich Kalus ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Tissue Donors ◽

Occult Hbv Infection ◽

Occult Hbv ◽

B Virus ◽

Immunodeficiency Virus

Background: Although transmission of pathogenic viruses through human tissue grafts is rare, it is still one of the most serious dreaded risks of transplantation. Therefore, in addition to the detailed medical and social history, a comprehensive serologic and molecular screening of the tissue donors for relevant viral markers for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) is necessary. In the case of reactive results in particular, clear decisions regarding follow-up testing and the criteria for tissue release must be made. Methods: Based on the clinical relevance of the specific virus markers, the sensitivity of the serological and molecular biological methods used and the application of inactivation methods, algorithms for tissue release are suggested. Results: Compliance with the preanalytical requirements and assessment of a possible hemodilution are mandatory requirements before testing the blood samples. While HIV testing follows defined algorithms, the procedures for HBV and HCV diagnostics are under discussion. Screening and decisions for HBV are often not as simple, e.g., due to cases of occult HBV infection, false-positive anti-HBc results, or early window period positive HBV NAT results. In the case of HCV diagnostics, modern therapies with direct-acting antivirals, which are often associated with successful treatment of the infection, should be included in the decision. Conclusion: In HBV and HCV testing, a high-sensitivity virus genome test should play a central role in diagnostics, especially in the case of equivocal serology, and it should be the basis for the decision to release the tissue. The proposed test algorithms and decisions are also based on current European recommendations and standards for safety and quality assurance in tissue and cell banking.

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