High-throughput approaches to unravel hepatitis C virus-host interactions

Colpitts, Che C.; El-Saghire, Hussein; Pochet, Nathalie; Schuster, Catherine; Baumert, Thomas F.

doi:10.1016/j.virusres.2015.09.013

Cited by 9 publications

(11 citation statements)

References 78 publications

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“…During the last decade, improvements in the understanding of the viral life cycle have resulted in development of direct-acting antivirals (DAAs) [reviewed by Dubuisson and Cosset [ 58 ] and Scheel and Rice [ 59 ] however, there are still many issues that are associated with HCV treatment. These barriers include high percentage of patients who are unaware of their infection, limited access to therapy, high cost, successful HCV treatment does not eliminate the HCC risk, [ 60 , 61 ] genotypic efficacy and occasional occurrence of resistance-associated variants. [ 62 ] The recent clinical licensing of DAAs enables viral cure.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, once fibrosis is established, curing HCV infection does not eliminate the risk for HCC. [ 61 ] It would be interesting to investigate the effectiveness of the recently developed antivirals in Pakistani HCV infected patients, in the current transition phase from IFN + RBV to DAA combinations. However, so far there is no published study in this direction.…”

Section: Resultsmentioning

confidence: 99%

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A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges

et al. 2016

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Background:The estimated hepatitis C virus (HCV) carriers are approximately 10 million in Pakistan which usually progresses to chronic hepatitis, with rare cases of spontaneous viral eradication. The present article reviews the treatment status of HCV infection in Pakistani population and various factors associated with the treatment response rates.Methods:Literature on anti-HCV therapy was searched in PubMed, Google Scholar and PakMediNet. Thirty three different studies representing different geographic regions of Pakistan published from 2002 to 2016 were included in the present review. Weighted mean, standard error estimates (SE) and standard deviation (SD) were determined for each population group.Results:Mean value for sustained virological response (SVR) for standard IFN plus ribavirin (RBV) combination therapy was 68.38% ± 14.13% (range 33.8%–87.10%; SE 3.08) and pegylated-IFN plus RBV combination therapy 64.38% ± 8.68% (range 55.0%–76.00%; SE 3.88). The lowest value for SVR has been reported to be 24.3% (for genotype 1; administering INF-α 2b 3MU 3 times/week and RBV 1000–1200 mg/day for 48 weeks) while highest of 87.5% (genotype 3a; INF-α 2a 3MU 3 times/week and RBV 1000–1200 mg/day for 24 weeks). The mean value for rapid virological response (RVR) was found to be 48.18% ± 29.20% (SE 9.73). As PEG-interferon and direct acting antivirals (DAAs) are relatively expensive, interferon-alfa (IFN-α) and RBV combination therapy have been used widely to treat HCV infected patients in Pakistan for the last one and half decade. On average, 2.45% of the patients discontinued treatment due to severe side effects.Conclusion:We encourage further studies on understanding host and viral factors associated with specific focus on harder to treat viral variants (relapsers and nonresponders). These variants are currently rising in the country.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges

et al. 2016

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“…Thus, more precise characterization of both CNV regions in human genome and HCV-human interactome is still necessary to better elucidate the associations between CNV and the course of HCV infection. The problem of HCV-host interactions has been recently addressed by several research groups 63 64 65 . As a result, the size of the interactome has been increased from 421 to 969 human proteins 64 .…”

Section: Discussionmentioning

confidence: 99%

Copy number variation of genes involved in the hepatitis C virus-human interactome

Budzko

Marcinkowska-Swojak

Jackowiak

et al. 2016

Sci Rep

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Copy number variation (CNV) is a newly discovered form of intra-species genetic polymorphism that is defined as deletions or duplications of genome segments ranging from 1 kbp to several Mbp. CNV accounts for the majority of the genetic variation observed in humans (CNV regions cover more than 10% of the human genome); therefore, it may significantly influence both the phenotype and susceptibility to various diseases. Unfortunately, the impact of CNV on a number of diseases, including hepatitis C virus (HCV) infection, remains largely unexplored. Here, we analyzed 421 human genes encoding proteins that have been shown to interact with HCV proteins or genomic RNA (proteins from the HCV-human interactome). We found that 19 of the 421 candidate genes are located in putative CNV regions. For all of these genes, copy numbers were determined for European, Asiatic and African populations using the multiplex ligation-dependent amplification (MLPA) method. As a result, we identified 4 genes, IGLL1, MLLT4, PDPK1, PPP1R13L, for which the CN-genotype ranged from 1 to 6. All of these genes are involved in host-virus interaction; thus, their polymorphism has a potential impact on the development of HCV infection and/or therapy outcome.

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“…Development of cell culture systems producing HCV pseudoparticles (HCVpp) and infectious HCV particles (HCVcc) has shed light on HCV interactions and enabled discovery of antiviral drugs and vaccines (Colpitts et al, 2016). HCVpp consist of HCV E1 and E2 glycoproteins enveloping a retroviral particle that packages GFP mRNA during assembly (Bartosch et al, 2003).…”

Section: Assays and Methods For Screening And Evaluating Viral Entry mentioning

confidence: 99%

In vitro methods for testing antiviral drugs

Rumlová

Ruml

2018

Biotechnology Advances

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Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses.

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High-throughput approaches to unravel hepatitis C virus-host interactions

Cited by 9 publications

References 78 publications

A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges

A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges

Copy number variation of genes involved in the hepatitis C virus-human interactome

In vitro methods for testing antiviral drugs

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