HCV NS3 Genotype-6a
Description
Resistance-Associated Substitutions (RASs) in GT-6a NS3
RASs in the NS3 region influence treatment outcomes with DAAs. Below are key findings from studies on GT-6a:
Notes:
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Q80K: A common RAS in GT-1a, but also observed in GT-6a. It reduces susceptibility to simeprevir but not newer PIs like voxilaprevir .
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A156V/D168E: These mutations are rare in GT-6a but confer resistance to first-generation PIs .
Geographic Distribution and Prevalence
GT-6a is prevalent in Southeast Asia, particularly in China and Vietnam. Its distribution is distinct from other GT-6 subtypes:
| Region | HCV Genotype/Subtype | Prevalence (%) |
|---|---|---|
| Asia (China, Vietnam) | GT-6a | 3.0% (among 2937 patients) |
| Europe | GT-6a | Not reported (GT-6 subtypes are rare) |
Key Insight: GT-6a is less prevalent globally compared to GT-1a or GT-3a but remains significant in endemic regions .
In Vitro Susceptibility to DAAs
Studies evaluating HCV GT-6a’s response to DAAs reveal:
| Drug Class | Drug | EC₅₀ (nM) | Notes |
|---|---|---|---|
| NS3 Protease Inhibitors | Voxilaprevir | 0.52 (median) | High potency against GT-6 (including 6a) |
| NS5A Inhibitors | Ledipasvir | 0.1–19 (GT-6a consensus) | Susceptibility varies by NS5A polymorphisms |
Data Source: EC₅₀ values for voxilaprevir against GT-6 clinical isolates (median: 0.52 nM) indicate high susceptibility .
Comparative Analysis with Other GT-6 Subtypes
GT-6a differs from other GT-6 subtypes (e.g., 6b, 6f) in RAS prevalence and treatment response:
| Subtype | NS3 RASs | NS5A RASs | Clinical Relevance |
|---|---|---|---|
| GT-6a | Q80K (common) | L28 polymorphisms (rare) | Higher susceptibility to NS5A inhibitors |
| GT-6b | A156V/D168E (rare) | L28T-L31I (common) | Reduced NS5A inhibitor efficacy |
| GT-6f | Similar to GT-6b | L28T-R30S (common) | High NS5A inhibitor resistance |
Research Gaps and Future Directions
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Immunogenicity: Limited data exist on GT-6a NS3-specific T-cell epitopes. Studies on GT-6b suggest NS3 may influence immune evasion, but GT-6a-specific insights are lacking .
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Long-Term Resistance Monitoring: While GT-6a has fewer RASs, ongoing surveillance is needed to track emerging mutations, particularly in endemic regions .
Product Specs
Product Science Overview
Hepatitis C virus (HCV) is a significant global health concern, affecting millions of people worldwide. The virus is known for causing chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Among the various genotypes of HCV, genotype 6a is predominantly found in Southeast Asia. The non-structural protein 3 (NS3) of HCV plays a crucial role in the viral life cycle, making it a target for therapeutic interventions. This article delves into the background of the recombinant NS3 protein of HCV genotype 6a, specifically the amino acid sequence 1192-1459.
The NS3 protein of HCV is a multifunctional enzyme with protease and helicase activities. The protease domain, located at the N-terminus, is responsible for cleaving the viral polyprotein into functional units, essential for viral replication. The helicase domain, situated at the C-terminus, unwinds the viral RNA, facilitating replication and translation. The recombinant NS3 protein, encompassing amino acids 1192-1459, includes the helicase domain, which is vital for the virus’s replication machinery .
HCV genotype 6a is one of the most diverse and complex genotypes, with a high prevalence in Southeast Asia. This genotype is known for its resistance to certain antiviral therapies, making it a challenging target for treatment. The study of the NS3 protein in genotype 6a is crucial for understanding the virus’s resistance mechanisms and developing effective therapeutic strategies .
The recombinant NS3 protein of HCV genotype 6a, specifically the amino acid sequence 1192-1459, is produced using bacterial expression systems. The gene encoding this protein is cloned into a suitable vector and expressed in Escherichia coli. The expressed protein is then purified using affinity chromatography techniques. This recombinant protein is used in various research applications, including the study of enzyme kinetics, inhibitor screening, and structural analysis .
The recombinant NS3 protein is a valuable tool in HCV research. It is used to study the enzyme’s structure and function, providing insights into the viral replication process. Additionally, the protein is employed in screening assays to identify potential inhibitors that can block the helicase activity, offering a pathway for developing new antiviral drugs. The recombinant NS3 protein also serves as an antigen in diagnostic assays, aiding in the detection of HCV infections .
