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Evolution of hypervariable region 1 of hepatitis C virus in primary infection
A Manzin1, L Solforosi, E Petrelli
1Istituto di Microbiologia, Università di Ancona, Ancona, Italy. manzin@popcsi.unian.it
Insights
Hepatitis C virus (HCV) hypervariable region 1 (HVR-1) evolution during primary infection suggests an oligoclonal event. Host selective pressure drives distinct viral genetic adaptations for persistence.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Hepatitis C virus (HCV) infection remains a significant global health concern.
- Understanding viral evolution during acute infection is crucial for developing effective treatments.
- The hypervariable region 1 (HVR-1) of the HCV E2 envelope protein is a key target for host immune responses.
Purpose of the Study:
- To investigate the dynamics of intrahost HCV variability during primary infection.
- To determine the role of host selective pressure in driving HCV genetic evolution.
- To analyze HVR-1 sequence variations in sequential samples from patients with acute hepatitis C.
Main Methods:
- Analysis of HVR-1 sequences from 20 clones per time point in sequential samples from three patients.
- Amplification, cloning, and purification of plasmid DNA from transformed cells.
- Intrasample and intersample evolutionary analyses including Ka, Ks, Ka/Ks ratio, and genetic distances.
Main Results:
- Low genetic distances in early HVR-1 samples, decreasing further after seroconversion, indicating an oligoclonal origin of primary HCV infection.
- Differential levels and dynamics of host selective pressure observed across the three cases.
- Intersample analysis confirmed individual HCV genetic evolution patterns, highlighting varied contributions of neutral evolution and selective forces.
Conclusions:
- Primary HCV infection is likely an oligoclonal event.
- Host selective pressure plays a significant role in shaping viral genetic diversity during acute infection.
- HCV adaptation for in vivo persistence involves diverse evolutionary routes, reflecting viral fitness in individual host environments.
Abstract:
The hypervariable region 1 (HVR-1) of the putative envelope encoding E2 region of hepatitis C virus (HCV) RNA was analyzed in sequential samples from three patients with acute type C hepatitis infected from different sources to address (i) the dynamics of intrahost HCV variability during the primary infection and (ii) the role of host selective pressure in driving viral genetic evolution. HVR-1 sequences from 20 clones per each point in time were analyzed after amplification, cloning, and purification of plasmid DNA from single colonies of transformed cells. The intrasample evolutionary analysis (nonsynonymous mutations per nonsynonymous site [Ka], synonymous mutations per synonymous site [Ks], Ka/Ks ratio, and genetic distances [gd]) documented low gd in early samples (ranging from 2. 11 to 7.79%) and a further decrease after seroconversion (from 0 to 4.80%), suggesting that primary HCV infection is an oligoclonal event, and found different levels and dynamics of host pressure in the three cases. The intersample analysis (pairwise comparisons of intrapatient sequences; rKa, rKs, rKa/rKs ratio, and gd) confirmed the individual features of HCV genetic evolution in the three subjects and pointed to the relative contribution of either neutral evolution or selective forces in driving viral variability, documenting that adaptation of HCV for persistence in vivo follows different routes, probably representing the molecular counterpart of the viral fitness for individual environments.