Hepatitis C virus (HCV) genotype 1b displays higher genetic variability of hypervariable region 1 (HVR1) than...

Area of Science:

• Virology
• Genetics
• Infectious Diseases

Background:

• Hepatitis C virus (HCV) exhibits significant genetic variability within hosts.
• The impact of this variability on the clinical course of HCV infection remains unclear.
• The hypervariable region 1 (HVR1) is a key area of HCV genetic diversity.

Purpose of the Study:

• To investigate the genetic variability of HCV HVR1 in genotypes 1b and 3.
• To compare HVR1 variability in early seronegative (HCV-RNA+, anti-HCV-) and chronic infection stages.
• To determine if observed variability differences are inherent to specific HCV genotypes.

Main Methods:

• Next-generation sequencing was employed to analyze HCV HVR1 genetic variability.
• ShoRAH software was used for sequencing error correction and haplotype inference.
• DNA SP and MEGA software were utilized to assess genetic diversity parameters.

Main Results:

• Genotype 3 showed significantly lower intra-host variant numbers during early infection compared to genotype 1b (p < 0.02).
• Chronic genotype 3 infections also exhibited significantly lower variant numbers, nucleotide substitutions, and diversity per site than genotype 1b (p < 0.0005).
• Early HCV infection displayed significantly lower HVR1 variability than chronic infection for both genotypes (p < 0.04).

Conclusions:

• HCV genotype 3 demonstrates inherently lower HVR1 genetic variability compared to genotype 1b.
• This reduced variability in genotype 3 is evident in both early and chronic stages of infection.
• The findings suggest that genetic background influences HCV HVR1 variability during infection.