Abstract
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.
Highlights
The hepatitis C virus (HCV) is the leading cause of liver disease with over 170 million people infected
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
Over the last ten years, HCV genotype 4 was identified with reverse hybridization in 172 serum samples (3.3%) from a cohort of 5197 HCV-infected patients who attended the General Hospital of Palermo
Summary
The hepatitis C virus (HCV) is the leading cause of liver disease with over 170 million people infected. HCV is classified by eight genotypes (1–8) and 90 subtypes according to the International. HCV genotype 4 (HCV-4) accounts for 12–15% of worldwide HCV infections (15–18 million), showing a prevalence of 1% and 10–20% in the USA and Europe, respectively. It dominates in North-Central Africa and in Arabic countries, such as Egypt, Lebanon, Syria, Saudi Arabia, and Kuwait [1,2], where a large population is HIV/HCV co-infected and access to care is limited [3]. In Egypt, subtype 4a accounts for the majority of HCV infections and its high prevalence is probably due to the unsafe use of injections during the past anti-schistosomal public health campaigns [4].
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