Mutations in the E2 and NS5A regions in patients infected with hepatitis C virus genotype 1a and their correlation with response to treatment

Abstract

Heterogeneity of subgenomic regions of hepatitis C virus (HCV) may be associated with response to interferon (IFN) therapy. The amino acid sequences of the PKR/eIF-2α phosphorylation homology domain (pePHD), IFN sensitivity determining region (ISDR), PKR binding domain (PKRBD), and variable region 3 (V3) were studied in 19 patients before and after 4 weeks of treatment. All patients were infected with HCV genotype 1a and were treated with pegylated-IFN and ribavirin. Thirteen patients achieved sustained viral response (responders) and six failed to clear viral RNA (nonresponders). The amino acid sequences in the pePHD and ISDR were identical in responders and nonresponders. However, amino acid substitution at position 2252 of PKRBD was significantly different between responders and nonresponders (P = 0.044). A larger number of mutations were observed in the V3 region of responders (P < 0.001). In this region, the amino acid in position 2364 differed between responders and nonresponders (responders: aspartic acid and serine, nonresponders: asparagine, P = 0.018). The amino acid sequences in the regions which were studied did not change after 4 weeks of treatment. It is concluded that the presence of specific amino acids in position 2252 of PKRBD and position 2364 of V3 might be associated with clinical response to IFN.

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran

“…Consistent with other studies (6, 41), our findings showed that genotype 3 followed by genotypes 1 and 2 were dominant in responder subjects, and genotypes 1 and 3 were the most frequent genotypes in non-responder patients.…”

“…With the current treatment regimen, pegylated interferon (PEG-IFN) plus ribavirin, sustain virological response (SVR) is achieved in only 50% of infected individuals (4). A number of factors including age, alcohol consumption, viral genotype, duration of infection, and viral load have been assigned variable significances in determining the response to antiviral treatment (5, 6). However, the emerging field of immunogenetic has confirmed the significant role of heredity in host immune response to infections (7, 8).…”

Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C Virus In Vitro Associated with Increased Viral Fitness and Interferon Resistance

“…Sequence variation of NS5A ISDR received considerable attention as a determinant of IFN resistance, mainly for Japanese genotype 1b isolates (67,68). However, other studies, including a study of patients with viral breakthrough during IFN treatment (61), suggested that sequence variation in other NS5A regions is associated with IFN treatment response (7,8,69). Of note, previously developed JFH1-based recombinants with 1b(J4) NS5A with and without sensitive-type ISDR mutations (46) responded similarly to IFN-␣ in experiments similar to those shown in Fig.…”

Analysis of the PKR-eIF2alpha phosphorylation homology domain (PePHD) of hepatitis C virus genotype 1 in HIV-coinfected patients by ultra-deep pyrosequencing and its relationship to responses to pegylated interferon-ribavirin treatment

“…Many authors have reported that HCV-E2-PePHD is a highly conserved region [23,24,[27][28][29][30][31][32][33][34][35], but none of them described these results in patients coinfected with HIV. Gaudy et al [26] found a high degree of conservation of HCV-E2-PePHD in monoinfected patients with genotype 1b and no association between HCV-E2-PePHD mutations and response to treatment, while Yahoo et al [34] reported high amino acid conservation in HCV-1a at four weeks of treatment.…”

“…Gaudy et al [26] found a high degree of conservation of HCV-E2-PePHD in monoinfected patients with genotype 1b and no association between HCV-E2-PePHD mutations and response to treatment, while Yahoo et al [34] reported high amino acid conservation in HCV-1a at four weeks of treatment. The effect of HIV infection on PEG-IFN?RBV therapy outcome could produce changes in T-cell subsets.…”