Sequence variation of the HVR1 region of Hepatitis C virus in response to interferon-α and ribavirin treatment

Al‐Qahtani, Ahmed; Rubino, Salvatore; Al‐Ahdal, Mohammed N.

doi:10.3855/jidc.1806

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…Extracted RNA was converted to cDNA as described before by Al-Qahtani et al [18] and subgenotypes were determined according to the procedures described by Murphy et al [19]. PCR products were sequenced using BigDye Terminator v3.1 cycle sequencing Kit (Applied Biosystems, Foster City, CA, USA) following manufacturer's recommendations.…”

Section: Methodsmentioning

confidence: 99%

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Al‐Qahtani

Al-Anazi

Abdo

et al. 2015

Journal of Immunology Research

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Recent studies have demonstrated that polymorphisms near the interleukin-28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B serum level was detected and variations at five single nucleotide polymorphisms (SNPs) in IL28B gene region were genotyped and analyzed. The variation of IL28B genetic polymorphisms was found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all P values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (P = 0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P = 0.005 and 0.003, resp.). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. This study indicates that variation at SNP rs8099917 could predict the serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level may serve as a useful marker for the development of HCV-associated sequelae.

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Section: Methodsmentioning

confidence: 99%

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Al‐Qahtani

Al-Anazi

Abdo

et al. 2015

Journal of Immunology Research

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“…Extracted RNA was converted to cDNA as described before. [13] Subgenotyping was performed according to the procedures described by Murphey et al . [14] PCR product were sequenced using BigDye ® Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems, Foster City, CA, USA) following manufacturer's recommendations.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis C genotype 4: Genotypic diversity, epidemiological profile, and clinical relevance of subtypes in Saudi Arabia

Ashgar

Khan

Al-Ahdal

et al. 2013

Saudi J Gastroenterol

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Background/Aim:Hepatitis C virus genotypes 4 (HCV-4) is the most prevalent genotype in Saudi Arabia, although it's various subtypes, mode and route of transmission remains unknown. The aim of this study was to analyze (i) the variability of the HCV-4 subtypes, the route and source of HCV transmission and (ii) the influence of HCV-4 subtypes on their therapeutic response.Patients and Methods:Sixty-four HCV-4 patients were analyzed retrospectively for the prevalence of various sub-genotypes and the possible mode of transmission, and it was correlated with their treatment response to pegylated interferon (PEG-IFN) α-2a and ribavirin therapy.Results:Positive history of blood or blood products transfusion was noted in 22 patients (34%), hemodialysis in 10 patients (15.6%), surgery in 7 patients (11%), and unknown etiology in 25 patients (39%). Prevalence of HCV-4 subtypes was 4a = 48.4% (31/64), 4d = 39% (25/64), 4n = 6.25% (4/64), and remaining combined (4m, 4l, 4r, 4o) 6.25% (4/64). No significant correlation between subtypes and the source of transmission was recognized (P = 0.62). Sustained virological response in all HCV-4 patients was 64% (41/64), while in each subtypes separately it was 4a 77.4% (24/31), 4d 52% (13/25), and combined (4n, 4m, 4l, 4r, 4o) 62.5% (5/8) (P = 0.046).Conclusion:No obvious cause for the mode of HCV transmission was noted in majority of the patients. No significant correlation was observed between HCV-4 subtypes and the source of HCV infection. 4a and 4d subtypes were the most common in Saudi Arabia, and patients infected with 4a subtype responded significantly better to combination therapy than to 4d subtype.

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“…HCV evades the adaptive antibody response through the acquisition of immune escape mutations. The majority of these mutations are within HVR1 suggesting it is immunodominant [ 16 – 19 ]. In addition, glycoprotein E2 is extensively glycosylated and these glycans can mask neutralization epitopes [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Sequence and Functional Evolution within Glycoprotein E2 in Hepatitis C Virus Genotype 3a Infection

et al. 2015

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The E2 glycoprotein of Hepatitis C virus (HCV) is a major target of the neutralizing antibody (NAb) response with the majority of epitopes located within its receptor binding domain (RBD; 384–661). Within E2 are three variable regions located at the N-terminus (HVR1; 384–411), and internally at 460–480 (HVR2) and 570–580 [intergenotypic variable region (igVR)], all of which lie outside a conserved core domain that contains the CD81 binding site, essential for attachment of virions to host cells and a major target of NAbs. In this study, we examined the evolution of the E1 and E2 region in two patients infected with genotype 3a virus. Whereas one patient was able to clear the acute infection, the other developed a chronic infection. Mutations accumulated at multiple positions within the N-terminal HVR1 as well as within the igVR in both patients over time, whereas mutations in HVR2 were observed only in the chronically infected patient. Mutations within or adjacent to the CD81 contact site were observed in both patients but were less frequent and more conservative in the patient that cleared his/her infection. The evolution of CD81 binding function and antigenicity was examined with longitudinal E2 RBD sequences. The ability of the RBD to bind CD81 was completely lost by week 108 in the patient that developed chronic HCV. In the second patient, the ability of the week 36 RBD, just prior to viral clearance, to bind CD81 was reduced ~50% relative to RBD sequences obtained earlier. The binding of a NAb specific to a conserved epitope located within E2 residues 411–428 was significantly reduced by week 108 despite complete conservation of its epitope suggesting that E2 antigenicity is allosterically modulated. The exposure of non-neutralizing antibody epitopes was similarly explored and we observed that the epitope of 3 out of 4 non-NAbs were significantly more exposed in the RBDs representing the late timepoints in the chronic patient. By contrast, the exposure of non-neutralizing epitopes was reduced in the patient that cleared his/her infection and could in part be attributed to sequence changes in the igVR. These studies reveal that during HCV infection, the exposure of the CD81 binding site on E2 becomes increasingly occluded, and the antigenicity of the E2 RBD towards both neutralizing and non-neutralizing antibodies is modulated via allosteric mechanisms.

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Sequence variation of the HVR1 region of Hepatitis C virus in response to interferon-α and ribavirin treatment

Cited by 6 publications

References 39 publications

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Hepatitis C genotype 4: Genotypic diversity, epidemiological profile, and clinical relevance of subtypes in Saudi Arabia

Longitudinal Sequence and Functional Evolution within Glycoprotein E2 in Hepatitis C Virus Genotype 3a Infection

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