Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition
Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/12/1363 |
| _version_ | 1797546408345075712 |
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| author | Giuseppina Maria Elena Colomba Noemi Urone Vito di Marco Donatella Ferraro |
| author_facet | Giuseppina Maria Elena Colomba Noemi Urone Vito di Marco Donatella Ferraro |
| author_sort | Giuseppina Maria Elena Colomba |
| collection | DOAJ |
| description | Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients naïve to DAA therapy was evaluated. We found that the presence of resistance-associated substitutions (RAS) was able to affect drug responses. Next, using a prediction tool, viral mutations were identified by their ability, or lack thereof, to reduce the binding affinity with HLA, which affects T cell recognition. The Bayesian coalescent analysis suggested two different circulation clusters, one in risk groups (IDUs and MSM) and the other due to migration flows, dated to 1940 and 1915, respectively. Most of the RAS overlapped with HLA and a lack of binding mutations was observed in 96% of strains. This study describes the introduction of HCV genotype 4 in a region of the Mediterranean basin and evaluates how HCV genotype 4’s genetic variability could affect the response of antiviral drugs and CD8+ T cell recognition. |
| first_indexed | 2024-03-10T14:28:20Z |
| format | Article |
| id | doaj.art-9c7caa9c69ee4f27a2957a5f423cfeb9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T14:28:20Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-9c7caa9c69ee4f27a2957a5f423cfeb92023-11-20T22:46:57ZengMDPI AGViruses1999-49152020-11-011212136310.3390/v12121363Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell RecognitionGiuseppina Maria Elena Colomba0Noemi Urone1Vito di Marco2Donatella Ferraro3Dipartimento di Scienze per la Promozione della Salute, Materno-Infantile di Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro”, 90133 Palermo, ItalyDipartimento di Scienze per la Promozione della Salute, Materno-Infantile di Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro”, 90133 Palermo, ItalyDipartimento di Scienze per la Promozione della Salute, Materno-Infantile di Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro”, 90133 Palermo, ItalyDipartimento di Scienze per la Promozione della Salute, Materno-Infantile di Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro”, 90133 Palermo, ItalyTherapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients naïve to DAA therapy was evaluated. We found that the presence of resistance-associated substitutions (RAS) was able to affect drug responses. Next, using a prediction tool, viral mutations were identified by their ability, or lack thereof, to reduce the binding affinity with HLA, which affects T cell recognition. The Bayesian coalescent analysis suggested two different circulation clusters, one in risk groups (IDUs and MSM) and the other due to migration flows, dated to 1940 and 1915, respectively. Most of the RAS overlapped with HLA and a lack of binding mutations was observed in 96% of strains. This study describes the introduction of HCV genotype 4 in a region of the Mediterranean basin and evaluates how HCV genotype 4’s genetic variability could affect the response of antiviral drugs and CD8+ T cell recognition.https://www.mdpi.com/1999-4915/12/12/1363phylodynamicHCVgenotype 4DAABayesian analysisviral epitopes |
| spellingShingle | Giuseppina Maria Elena Colomba Noemi Urone Vito di Marco Donatella Ferraro Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition Viruses phylodynamic HCV genotype 4 DAA Bayesian analysis viral epitopes |
| title | Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition |
| title_full | Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition |
| title_fullStr | Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition |
| title_full_unstemmed | Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition |
| title_short | Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition |
| title_sort | phylodynamic analysis and implication of hcv genotype 4 variability on antiviral drug response and t cell recognition |
| topic | phylodynamic HCV genotype 4 DAA Bayesian analysis viral epitopes |
| url | https://www.mdpi.com/1999-4915/12/12/1363 |
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