Role of different regions of the hepatitis C virus genome in the therapeutic response to interferon-based treatment

Khaliq, Saba; Latief, Noreen; Saleem, Sidrah

doi:10.1007/s00705-013-1780-x

Cited by 7 publications

(4 citation statements)

References 164 publications

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“…Interferons are natural cellular proteins with a number of immune functions including induction of the antiviral state, secretion of cytokines, enrolment of immune cells, and induction of cell differentiation. IFN-a can normalize liver function tests (LFT) results and improve hepatic inflammation by interfering with viral replication in patients with HCV infection [17]. In treating infection with Peg-IFN-a2b and ribavirin, knowledge of a patient's viral genotype is very important as it determines the duration of the therapy [2].…”

Section: Phylogenetic Tree and Secondary Structure Prediction Of Iresmentioning

confidence: 99%

“…Accession no. ofDiscussion HCV infection is considered a significant risk factor for development of hepatocellular carcinoma (HCC) [7,17]. Nucleotide substitutions in the viral genome result in its diversity into quasispecies, subtypes and distinct genotypes.…”

Section: Phylogenetic Tree and Secondary Structure Prediction Of Iresmentioning

confidence: 99%

“…Nucleotide substitutions in the viral genome result in its diversity into quasispecies, subtypes and distinct genotypes. The various genotypes differ in their infectivity and immune response due to these nucleotide variations [17].…”

Section: Phylogenetic Tree and Secondary Structure Prediction Of Iresmentioning

confidence: 99%

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Frequency of nucleotide sequence variations in the internal ribosome entry site region of hepatitis C virus RNA isolated from responding and non-responding patients with hepatitis C virus genotype 3 infection

et al. 2016

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Located within 5 0 untranslated region of HCV RNA is internal ribosome entry site (IRES) which directs cap-independent translation of viral polyprotein. Mutations in IRES sequence have been shown to cause changes in efficiency of protein translation in vitro in few instances. No study has been done to investigate association between frequency of nucleotide sequence variations in IRES region of HCV-3 RNA and response to pegylated interferon-a plus ribavirin therapy. Hence, this study was planned to analyze relationship between frequency of nucleotide sequence variations of HCV-3 IRES region and response to therapy. Twenty-seven HCV-3 patients were studied, of whom 19 responded to therapy and 8 did not. Alanine aminotransferase and aspartate aminotransferase levels were significantly lower in responders compared to non-responders. HCV RNA detection and genotyping was performed by nested-PCR and RFLP respectively. Viral load quantification in pre and post therapy samples was done by real time PCR. The viral load was significantly lower in the patients after treatment as compared to before treatment. HCV IRES region from pre-treatment sera of 27 HCV-3 infected patients was amplified by nested PCR and sequenced. Secondary structure of IRES region of HCV-3 was predicted using the M fold Web Server. Mutational analysis revealed hot spot of mutations in HCV-3 IRES region from 40-80 and 210-280 nucleotides. Though more mutations were found in non-responders as compared to responders, this difference was statistically insignificant. Therefore, in addition to IRES region of HCV-3, some other host and viral factors may contribute to therapy outcome.

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Section: Phylogenetic Tree and Secondary Structure Prediction Of Iresmentioning

confidence: 99%

Section: Phylogenetic Tree and Secondary Structure Prediction Of Iresmentioning

confidence: 99%

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Frequency of nucleotide sequence variations in the internal ribosome entry site region of hepatitis C virus RNA isolated from responding and non-responding patients with hepatitis C virus genotype 3 infection

et al. 2016

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“…NS5a'da yer alan V3 bölgesindeki değişiklikler de, bazı gruplarda tedavi yanıtı ile bağlantılı olarak izlenmiş; bunun muhtemel nedeninin, NS5a'nın PKRBD/ISDR gibi fonksiyonel bölgelerinde ortaya çıkan modifi kasyonlar olduğu öne sürülmüştür. V3 bölgesinde izlenen mutasyonların, konağın cinsiyeti ile ilişkisi ve kadınlarda daha az olması, konak ve virusun genetik özelliklerinin etkileşimini gösteren ilginç bir bulgudur 4,8,11,30,31 .…”

Section: Anti̇vi̇raller Ve Hcv Varyasyonlariunclassified

Clinical Impact of Hepatitis C Virus Genomic Variations

Ergünay¹,

Abacioglu²

2015

Mikrobiyol Bul

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Hepatitis C virus (HCV) is a globally-dispersed agent of chronic hepatitis with a significant public health threat, affecting over 110 million individuals throughout the world. The increased risk for chronicity after exposure and the lack of a protective vaccine make HCV is a leading infectious cause of cirrhosis, liver failure requiring transplantation and hepatocellular carcinoma. The replicative process and infection dynamics in the host enable HCV to generate an array of closely-related but non-identical genetic variants known as quasispecies in the infected individuals. Pathogenesis and outcome in HCV infections are directly affected by the virus genetic heterogeneity, reflected as the emergence of quasispecies in infected individuals. The evolution of these highly-diverse viral populations in the host directly influences the disease course, via providing a pool of variants capable of resuming viral replication under extrinsic and/or intrinsic selective pressures. Viral quasispecies go through several alterations during the course of the infection, and provide a background for the selection of escape mutants from the host humoral and cell-mediated immune responses and antiviral treatment. Supported by the robust next generation sequencing techniques, recent studies have provided significant insights on the genomic diversity and progression as well as on the origin and the epidemiology of HCV. This review provides an overview of the mechanisms of HCV genetic variability, and the interactions with the host, that affects clinical disease, covering viral and host determinants of humoral and cell-mediated immune responses, alterations during the early and late stages of the infection and disease progression leading to chronicity. In addition, current findings in virus evolution and epidemiology were briefly interpreted from the inter-species and population perspectives. The impact of viral genomic heterogeneity on antiviral treatment in the era of direct-acting agents is also discussed, along with an overview of current methods employed for the characterization of viral diversity.

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Genetic Variability of Hepatitis C Virus (HCV) 5’ Untranslated Region in HIV/HCV Coinfected Patients Treated with Pegylated Interferon and Ribavirin

et al. 2015

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Association between hepatitis C virus (HCV) quasispecies and treatment outcome among patients with chronic hepatitis C has been the subject of many studies. However, these studies focused mainly on viral variable regions (E1 and E2) and usually did not include human immunodeficiency virus (HIV)-positive patients. The aim of the present study was to analyze heterogeneity of the 5'untranslated region (5'UTR) in HCV/HIV coinfected patients treated with interferon and ribavirin. The HCV 5’UTR was amplified from serum and peripheral blood mononuclear cells (PBMC) samples in 37 HCV/HIV coinfected patients treated for chronic hepatitis C. Samples were collected right before treatment, and at 2, 4, 6, 8, 12, 20, 24, 36, 44, 48, 60, and 72 weeks. Heterogeneity of the 5'UTR was analyzed by single strand conformational polymorphism (SSCP), cloning and sequencing. Sustained virological response (SVR) was achieved in 46% of analyzed HCV/HIV co-infected patients. Stable SSCP band pattern was observed in 22 patients (62.9%) and SVR rate among these patients was 23%. Decline in the number of bands and/or shift in band positions were found in 6 patients (17.1%), 5 (83%) of whom achieved SVR (p=0.009). A novel viral genotype was identified in all but one of these patients. In 5 of these 6 patients a new genotype was dominant. 5'UTR heterogeneity may correlate with interferon and ribavirin treatment outcome. In the analyzed group of HCV/HIV coinfected patients, viral quasispecies stability during treatment favored viral persistence, whereas decrease in the number of variants and/or emergence of new variants was associated with SVR. Among injection drug users (IDU) patients, a new genotype may become dominant during treatment, probably due to the presence of mixed infections with various strains, which have different susceptibility to treatment.

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Role of different regions of the hepatitis C virus genome in the therapeutic response to interferon-based treatment

Cited by 7 publications

References 164 publications

Frequency of nucleotide sequence variations in the internal ribosome entry site region of hepatitis C virus RNA isolated from responding and non-responding patients with hepatitis C virus genotype 3 infection

Frequency of nucleotide sequence variations in the internal ribosome entry site region of hepatitis C virus RNA isolated from responding and non-responding patients with hepatitis C virus genotype 3 infection

Clinical Impact of Hepatitis C Virus Genomic Variations

Genetic Variability of Hepatitis C Virus (HCV) 5’ Untranslated Region in HIV/HCV Coinfected Patients Treated with Pegylated Interferon and Ribavirin

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