The current standard of care (SoC) for chronic hepatitis C, i.e. the combination of a pegylated-interferon (PEG-IFN) with ribavirin (RBV), may activate underlying autoimmune conditions. Particularly, interferon (IFN) has been known to induce or exacerbate autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in hepatitis C virus patients. We describe ...

Abstract Although past work has documented relations between HIV/AIDS and negative affective symptoms and disorders, empirical work has only just begun to address explanatory processes that may underlie these associations. The current investigation sought to test the main and interactive effects of HIV symptom distress and anxiety sensitivity in relation ...

This study assessed psychological distress (PD) in men who have sex with men (MSM) accessing primary health clinics in Australia. Relationships between PD, HIV status and substance use were explored. A cross-sectional convenience sample of 250 MSM completed the Personality Assessment Screener (PAS). One-third (n = 83) scored in the ...

Developing and testing safer conception methods that reduce HIV transmission to HIV-seronegative partners in serodiscordant couples and reduce superinfection in HIV-seroconcordant couples is a crucial but often unaddressed component of HIV prevention programs. Most research has focused on developed-world settings, where "high-technology" assisted reproduction techniques are used for HIV-serodiscordant couples ...

SummaryBackground and objectives Hepatitis C virus (HCV) infection is associated with increased mortality and morbidity in end-stage renal failure (ESRF) patients. Despite a lower incidence and risk of transmission of HCV infection with peritoneal dialysis (PD), the optimal dialysis modality for HCV-infected ESRF patients is not known. The aim of ...

As a result of the efficacy of highly active antiretroviral therapy (HAART), patients with human immunodeficiency virus (HIV) can survive longer and are thus naturally prone to ageing-related degenerative disorders such as Parkinson's disease (PD). Managing PD and HIV in the same patient may be challenging, as HAART and levodopa ...

This paper examines the associations between male migration and mobility with HIV among married couples in India. Cross-sectional analyses of a nationally representative household survey conducted across all 29 states of India from 2005 to 2006 via the National Family Health Survey-3 (NFHS-3) included a subsample of 27,771 married couples ...

To investigate the expression of programmed death (PD)-1, PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC). Liver biopsies and HCC specimens from patients were collected and histologically examined. The expression of PD-1, PD-L1, and PD-L2 in biopsy specimens of ...

Accumulating evidence supports couple-based approaches for HIV/STI preventive interventions. Yet, to date, no studies have examined couple-based sexual risk reductions intervention specifically for men who have sex with men (MSM) from populations with elevated rates of HIV/STI transmission, such as black MSM and methamphetamine-involved MSM. We pilot tested-using a pre-/post-test ...

Dual threats of injection drug use and risky sexual practices continue to increase transmission of HIV and other sexually transmitted infections (STIs) among drug-using couples in low-income communities in the United States. To date, no effective HIV prevention interventions have focused exclusively on this population. Using a randomized controlled trial, ...

Many HIV discordant couples express a strong wish to conceive a child. Insemination with processed semen is offered to these couples in many countries. Given the very low level of transmission risk during fully suppressive antiretroviral therapy, we offered timed intercourse combined with pre-exposure prophylaxis to further reduce the transmission ...

BACKGROUND: Hepatitis B leads to chronic liver disease, cirrhosis, and hepatocellular cancer. Viral markers and other laboratory tests used in diagnosis and follow-up of chronic hepatitis B (CHB) do not correlate well with disease activity and liver histopathology. For this reason, alternative tests that indicate disease activity are needed. We ...

Summary.  The aim of the present study was to investigate the variability of hepatitis C virus (HCV) CD81 binding regions (CD81-1/2) in peripheral blood mononuclear cells (PBMC)-derived and serum-derived HCV-RNA samples. HCV-RNA was isolated from PBMC (10(4) cells) and serum samples from 37 patients chronically infected with HCV genotype 1a/1b ...

BACKGROUND: Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, despite of absence of detectable HBsAg, HBV-DNA is present in patient's peripheral blood. The aim of this study was to investigate components of humoral immunity during OBI as a possible measure of how patients respond ...

Natural history of liver cirrhosis is divided into compensated and decompensated stage. Traditionally, the markers of decompensated cirrhosis include ascites, variceal hemorrhage, hepatic encephalopathy and jaundice. The clinical importance of portal vein thrombosis (PVT) is increasingly recognized in patients with liver cirrhosis. The presence of PVT is not only an ...

Most incident HIV infections in sub-Saharan Africa occur between cohabiting, discordant, heterosexual couples. Though couples' voluntary HIV counseling and testing (CVCT) is an effective, well-studied intervention in Africa, <1% of couples have been jointly tested. We conducted cross-sectional household surveys in Kigali, Rwanda (n = 600) and Lusaka, Zambia (n = 603) to ascertain ...

Despite the improvements in HCV-therapy achieved in the last 20 years, the occurrence of high frequency of non-responders and of therapy-related side effects has lead to an ongoing interest in optimizing duration and dosage of current antiviral regimens as well as to the research and development of new antiviral treatment. ...

The current therapy for hepatitis C virus (HCV) infection has limited efficacy, in particular against the genotype 1 virus, and a range of side effects. In this context of high unmet medical need, more efficacious drugs targeting HCV nonstructural proteins are of interest. Here we describe 2'-deoxy-2'-spirocyclopropylcytidine (5) as a ...

In flaviviruses and hepatitis C virus (HCV), the NS3 gene encodes the N-terminal protease (NS3pro) and the C-terminal helicase (NS3hel). In HCV, the downstream NS4A is required for the NS3pro activity and exhibits a conserved EFDEMEE motif. To identify the role of this motif, we compared the ATPase and helicase ...

With the advent of efficient systems to propagate the hepatitis C virus (HCV) in cultured cells important new discoveries have been made. For instance, several molecules required for HCV infection of hepatocytes have been identified and first insights into the entry pathway have been gained. Ribonucleic acid (RNA) replication and ...

Hepatitis C virus (HCV) is a global health problem requiring novel approaches for effective treatment of this disease. The HCV NS5B polymerase has been demonstrated to be a viable target for the development of HCV therapies. β-d-2'-Deoxy-2'-α-fluoro-2'-β-C-methyl nucleosides are selective inhibitors of the HCV NS5B polymerase and have demonstrated potent ...

Background/aims The life cycle of hepatitis C virus (HCV) is intimately linked to the lipid metabolism of the host. In particular, HCV exploits the metabolic machinery of the lipoproteins in several steps of its life cycle such as circulation in the bloodstream, cell attachment and entry, assembly and release of ...

RNA interference (RNAi) is being evaluated as an alternative therapeutic strategy for hepatitis C virus (HCV) infection. The use of viral vectors encoding short hairpin RNAs (shRNAs) has been the most common strategy employed to provide sustained expression of RNAi effectors. However, overexpression and incomplete processing of shRNAs has led ...

The three variable regions of hepatitis C virus (HCV) glycoprotein E2 can be removed simultaneously from the E2 ectodomain (residues 384-661) without affecting folding or CD81 binding. In this study, we show that deletion of hypervariable region (HVR) 2 or the intergenotypic variable region (igVR) in the context of the ...

Approximately 2% of the worldwide population is infected with hepatitis C virus (HCV), the major causative agent of non-A, non-B hepatitis. Although substantial progress has been made in developing tools to dissect the viral life cycle, most in vitro studies rely on hepatoma cell lines, which are functionally disparate from ...

To evaluate the presence and cross-reactive antibodies against hypervariable region 1 (HVR1) in hepatitis C virus (HCV) infected patients and its relationship with the progression of the disease. Sixteen representative HVR1 proteins selected from a unique set of 1600 natural sequences were used to semiquantitate the cross-reactivity of HVR1 antibodies ...

Insulin resistance (IR) is a major predictor of treatment failure in patients with hepatitis C virus (HCV) infection treated with peginterferon/ribavirin. The aim of this study was to evaluate the short-term effect of an HCV protease inhibitor monotherapy on IR in parallel with an antiviral effect. In a phase 1b ...

The pressing need for broad-spectrum antivirals could be met by targeting host rather than viral processes. Cholesterol biosynthesis within the infected cell is one promising target for a large number of viral systems, including hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. Liposomes developed for intracellular, endoplasmic reticulum ...

Accumulating evidence suggests that certain features of hepatitis C virus (HCV), especially its high genetic variability, might be responsible for the low efficiency of anti-HCV treatment. Here, we present a bioinformatic analysis of HCV-1a populations isolated from 23 children with chronic hepatitis C (CHC) subjected to interferon-ribavirin therapy. The structures ...

Triggering and propagating an intracellular innate immune response is essential for control of viral infections. RNase L is a host endoribonuclease and a pivotal component of innate immunity that cleaves viral and cellular RNA within single-stranded loops releasing small structured RNAs with 5'-hydroxyl (5'-OH) and 3'-monophosphoryl (3'-p) groups. In 2007, ...

Hepatitis C virus (HCV) infection spreads primarily via contact with infected blood and can establish a persistent infection in 80% of infected individuals, progressively causing chronic liver disease that can lead to hepatocellular carcinoma or end-stage liver disease requiring a transplant. There is no vaccine, and current treatment with interferon ...

There are limited data on diversity within the hepatitis C virus polymerase (NS5B). In concordance with its key functional role during the life cycle, NS5B intrapatient variability was low. Moreover, differences between NS5B nonsynonymous (dN) and synonymous (dS) mutation rates (dN - dS) were positively correlated with CD4 cell count, ...

Host heat shock cognate 70 (Hsc70) protein is packaged into hepatitis C viral (HCV) particles as a structural component of the virus in the assembly process. It helps HCV RNA release into the cytoplasm in the next infection cycle. The goal of this study is to investigate whether chemically down-regulating ...

Hepatitis C virus (HCV) infection is a common cause of chronic liver disease and a serious threat to human health. The HCV NS3/4A serine protease is necessary for viral replication and innate immune evasion, and represents a well-validated target for specific antiviral therapy. We previously reported the isolation of single-chain ...

Hepatitis C virus (HCV) is a major cause of liver disease but the full impact of HCV infection on the hepatocyte is poorly understood. RNA sequencing (RNA-Seq) is a novel method to analyze the full transcriptional activity of a cell or tissue, thus allowing new insight into the impact of ...

There is no protective vaccine or effective drug against hepatitis C virus (HCV). Sustained virological response to INF/ribavirin treatment regimen has an efficiency of about 50%. Many patients worldwide have used traditional medicines and herbal medicine in particular. A laccase has been purified from oyster mushroom (Pleurotus ostreatus) to homogeneity ...

Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective and better tolerated therapies are urgently needed. HCV is a positive, single-stranded RNA virus with a 9.6 ...

HCV-JFH1 yields subclones that develop cytopathic plaques (Sekine-Osajima Y, et al., Virology 2008; 371:71). Here, we investigated viral amino acid substitutions in cytopathic mutant HCV-JFH1 clones and their characteristics in vitro and in vivo. The mutant viruses with individual C2441S, P2938S or R2985P signature substitutions, and with all three substitutions, ...

Hepatitis C virus (HCV) infection causes significant morbidity, and efficient mouse models would greatly facilitate virus studies and the development of effective vaccines and new therapeutic agents. Entry factors, innate immunity, and host factors needed for viral replication represent the initial barriers that restrict HCV infection of mouse cells. Experiments ...

Patients with chronic hepatitis C virus (HCV) infection show an increased incidence of nervous system disorders such as chronic fatigue syndrome, depression and cognitive dysfunction. It is unclear whether this is because of HCV replication in the brain and in peripheral neuronal cells or to more indirect effects of HCV ...

MicroRNAs are a recently discovered new class of important endogenous regulators of gene function. Aberrant regulation of microRNAs has been linked to various human diseases, most importantly cancer. Small molecule intervention of microRNA misregulation has the potential to provide new therapeutic approaches to such diseases. Here, we report the first ...

Hepatitis C virus afflicts approximately 180 million people worldwide and currently there are no direct acting antiviral agents available to treat this disease. Our first generation nucleoside HCV inhibitor, RG7128 has already established proof-of-concept in the clinic and is currently in phase IIb clinical trials. As part of our continuing ...

The search for effective Hepatitis C antiviral therapies has recently focused on host sterol metabolism and protein prenylation pathways that indirectly affect viral replication. However, inhibition of the sterol pathway with statin drugs has not yielded consistent results in patients. Here, we present a combination chemical genetic study to explore ...

The discovery of RNA interference (RNAi), and of all related RNA silencing processes, was one of the major breakthroughs and is currently changing our understanding of liver physiology and pathogenesis of liver disease. Furthermore, recent studies indicate that microRNAs (miRNAs) are a promising therapeutic target. Plant and insect organisms use ...

The hepatitis C virus (HCV) NS5B RNA polymerase facilitates the RNA synthesis step during the HCV replication cycle. Nucleoside analogs targeting the NS5B provide an attractive approach to treating HCV infections because of their high barrier to resistance and pan-genotype activity. PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine-5'-monophosphate, is a highly active ...

Analysis of progressive changes in hepatic gene expression that underlie hepatocarcinogenesis following hepatitis C virus (HCV) infection require examination of long-term cultures of normally differentiating primary human hepatocytes. We report a culture system of primary hepatocytes that support productive replication of infectious HCV. Hepatic functions were analyzed by reverse-transcription polymerase ...

Hepatitis C virus (HCV) is a global health problem. Designing therapeutic agents that target HCV's RNA genome remains challenging. HCV genomic RNA is large and highly structured with long-range genome-scale ordered RNA structures. Predicting the secondary- and tertiary-structure elements that reveal the accessibility of target sites within HCV RNA is ...

Host cell factors are critical to all stages of the hepatitis C virus (HCV) life cycle. While many cellular proteins that regulate HCV genome synthesis have been identified, the mechanisms engaged in this process are incompletely understood. To identify novel cellular proteins involved in HCV RNA replication, we screened a ...

Rong and colleagues have applied a mathematical model of hepatitis C virus (HCV) replication to experimental data from initial clinical investigations of HCV protease inhibitors. In this Perspective, we discuss how mathematical modeling and other modern translational research tools and approaches can be used to expedite drug development with well-designed ...

Several synthetic siRNAs were designed to target various regions of hepatitis C virus (HCV) replicon RNA. The antiviral efficacies of the siRNAs were compared using real time PCR and western blot assessment. siRNAs targeting either specific coding region of HCV NS3 or NS5B were the most efficacious in terms of ...