Higher dN/dS ratios in the HCV core gene, but not in the E1/HVR1 gene, are associated with human immunodeficiency virus-associated immunosuppression

Xu, Chunhui; Shen, Tao; Ji, Zheng; Tu, Jing; Zhang, Weidong; Lu, Fengmin

doi:10.1007/s00705-012-1390-z

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Our results were different, since the concordance (91.5%) and correlation (r = 0.816) were both lower. It is also of note that ratio of HCV-RNA/HCVAg log 10 levels reported in 16 Chinese co-infected patients [43] were lower and more homogeneous (1.78 ± 0.16; median 1.74) than in the present study (2.25 ± 0.88; median 1.98) and not different from those found in HCV-monoinfected subjects.…”

Section: Discussioncontrasting

confidence: 66%

“…Thus far, only 3 very recent studies have explored the behaviour of HCV antigen in HIV/HCV co-infections. Xu et al [43] have shown a higher variability of the HCV Core gene sequences and a more diversified HCV quasispecies population in association with the progressive decrease in the immune pressure caused by long-term HIV infection, but HIV co-infection did not seem to influence the correlation between HCV-RNA and HCVAg. In residents from a rural village in China Shen et al [42] have found a high correlation both in 129 HCV-only infected (r = 0.808) and in 98 patients with the double infection (r = 0.952).…”

Section: Discussionmentioning

confidence: 99%

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HCV core antigen and HCV-RNA in HIV/HCV co-infected patients with different HCV genotypes

Garbuglia

Monachetti

Galli³

et al. 2014

BMC Infect Dis

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BackgroundA good correlation between HCV core antigen (HCVAg) and different HCV-RNA assays has been described, but little data are available in HCV/HIV co-infection. We aimed to evaluate HCVAg in comparison with HCV-RNA and to determine their kinetics during antiviral treatment in selected HCV/HIV co-infected patients.Methods355 samples from 286 HCV/HIV co-infected subjects for whom HCV-RNA (Abbott RealTime) was requested were analysed also for HCVAg (Abbott ARCHITECT) in order to evaluate the correlation between the two parameters both in patients treated or untreated for chronic hepatitis C and according to different HCV genotypes. The differences between percentages were evaluated by chi square or Fisher’s exact test, while mean and median values were compared by Student’s t test or the Mann–Whitney test, respectively. All differences were considered significant for a p value <0.05.ResultsHCVAg was detectable on 288/315 sera (91.4%) positive for HCV-RNA and in 5 out of40 (12.5%) sera with undetectable HCV-RNA for a total concordance of 90.1%. The correlation was fair both in untreated (r = 0.742) and in treated (r = 0.881) patients and stronger for genotypes 1 and 4 than for genotype 3. Both HCV-RNA and HCVAg levels were significantly higher (p = 0.028 and p = 0.0098, respectively) in patients infected by genotype 1 than by genotype 3. The mean ratio of Log values between HCV-RNA (IU/mL) and HCVAg (fmol/liter) was 2.27 ± 1.09 in untreated and 2.20 ± 0.82 in treated patients (p = n.s.),consistent with a sensitivity of HCVAg corresponding to about 1,000 IU/mL of HCV-RNA, and ranged from 2.21 to 2.32 among HCV genotypes with no significant differences; five samples (1.4%; 2 genotype 1a or 1c, 3 genotype 3a) showed highly divergent values. The analysis of 18 monitoring profiles from patients treated with PEG-IFN and Ribavirin showed similar trends, except in one case in which relapse could be predicted by HCVAg and not by HCV-RNA.ConclusionThese results suggest that HCVAg represents an adequate tool for determining an ongoing HCV infection also in HIV co-infected patients, with lower costs and faster turnaround time than HCV-RNA.

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Section: Discussioncontrasting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

HCV core antigen and HCV-RNA in HIV/HCV co-infected patients with different HCV genotypes

Garbuglia

Monachetti

Galli³

et al. 2014

BMC Infect Dis

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“…Therefore, the observed differences between HIV-1B evolution in mono and coinfected children could be at least in part due to the differential selection pressures exerted by the patient’s immune system. Third, it has been reported that HIV-associated immunosuppression can increase d N / d S ratios in some HCV proteins but not in others 53 , 54 . Thus, we cannot exclude that the observed effect of HCV coinfection in d N − d S can differ across HIV-1B proteins.…”

Section: Discussionmentioning

confidence: 96%

Effect of HIV/HCV Co-Infection on the Protease Evolution of HIV-1B: A Pilot Study in a Pediatric Population

Domínguez‐Rodríguez

Rojas

McPhee

et al. 2018

Sci Rep

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This pilot study evaluates in pediatric patients the impact of HIV/HCV coinfection in the molecular evolution of the HIV-1 subtype B protease (HIV-1BPR). For this study, HIV-1B/HCV coinfected (15) and HIV-1B monoinfected (56) patients with available HIV-1B pol sequences were enrolled. Both groups of patients had comparable gender frequencies and average age, time of infection, antiretroviral treatment (ART) exposure and time under ART. Prevalence of drug resistance mutations (DRM), genetic diversity, number of synonymous (dS) and non-synonymous (dN) mutations per site and selection pressures (dN − dS) in the HIV-1BPR were estimated and compared between mono- and coinfected patients. Both HIV-1B populations presented similar genetic diversity (0.050 ± 0.02 vs. 0.045 ± 0.01) and dS (0.074 ± 0.03 vs. 0.078 ± 0.04). In turn, in coinfected patients the HIV-1BPR had higher dN (0.045 ± 0.01 vs. 0.024 ± 0.01) and dN-dS (−0.026 ± 0.02 vs. −0.048 ± 0.04) values, and less amino acid sites under purifying selection (4.2% vs. 42.1%) than in monoinfected patients. Accordingly, in co-infection with HCV, the HIV-1BPR sites 50, 53, 82, 84 and 88 - associated with resistance to PIs - were under neutral evolution, whereas these sites were under purifying selection in monoinfected patients. This pilot study suggests that HIV-1B may evolve differently in the presence than in the absence of HCV.

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“…2 ) and in turn of c-MYC, TBX3, AXIN2, FNDC3B and CCND1 genes (Figs 3 and 5 ) have been described in other strains of HCV genotypes 1 and 4. Residue Thr71 has been reported in 18 isolates of HCV genotype 4 in Gabon 16 and Ser64 natural mutation has been reported in a limited number of HCV genotype 1 clinical isolates 43 , 44 . Residues 64 and 71 are located in the hydrophilic and basic domain of mature core protein (domain D1, amino acids 1–118, Fig.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of the Wnt/β-catenin pathway by hepatitis C virus recombinants expressing core from various genotypes

Aicher

Kakkanas

Cohen

et al. 2018

Sci Rep

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Clinical studies have suggested association of some hepatitis C virus (HCV) subtypes or isolates with progression toward hepatocellular carcinoma (HCC). HCV core protein has been reported to interfere with host Wnt/β-catenin pathway, a cell fate-determining pathway, which plays a major role in HCC. Here, we investigated the impact of HCV core genetic variability in the dysregulation of Wnt/β-catenin pathway. We used both transient expression of core proteins from clinical isolates of HCV subtypes 1a (Cambodia), 4a (Romania) and 4f (Cameroon) and infection systems based on a set of engineered intergenotypic recombinant viruses encoding core from these various clinical strains. We found that TCF transcription factor-dependent reporter activity was upregulated by core in a strain-specific manner. We documented core sequence-specific transcriptional upregulation of several β-catenin downstream target genes associated with cell proliferation and malignant transformation, fibrogenesis or fat accumulation. The extent of β-catenin nuclear translocation varied in accordance with β-catenin downstream gene upregulation in infected cells. Pairwise comparisons of subgenotypic core recombinants and mutated core variants unveiled the critical role of core residues 64 and 71 in these dysregulations. In conclusion, this work identified natural core polymorphisms involved in HCV strain-specific activation of Wnt/β-catenin pathway in relevant infection systems.

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Higher dN/dS ratios in the HCV core gene, but not in the E1/HVR1 gene, are associated with human immunodeficiency virus-associated immunosuppression

Cited by 5 publications

References 27 publications

HCV core antigen and HCV-RNA in HIV/HCV co-infected patients with different HCV genotypes

HCV core antigen and HCV-RNA in HIV/HCV co-infected patients with different HCV genotypes

Effect of HIV/HCV Co-Infection on the Protease Evolution of HIV-1B: A Pilot Study in a Pediatric Population

Differential regulation of the Wnt/β-catenin pathway by hepatitis C virus recombinants expressing core from various genotypes

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