The HCV genome consists of a positive 9.6 kb single-strand of RNA. Nucleotide substitutions in the HCV genome are common and a 2 kb deletion has been reported.
Methods
A total of 117 chronic hepatitis C (CHC) patients who were treated with pegylated interferon plus ribavirin combination therapy were enrolled in this study. Total RNA was extracted from the patients’ sera and reverse transcription and PCR were performed. Statistical analysis was performed to evaluate the effects of HCV deletion mutants on treatment with combination therapy.
Results
By amplifying entire HCV genomes using longdistance PCR, novel large deletion mutants were identified. Sequence analysis revealed that these deletions extended approximately 6 kb from the core/E2 region to the NS5A region and that there are three kinds of deletions that are identical at their 3′ and 5′ extremities. The subgenome virus particles appeared to coexist with full-genome virus particles in the sera of CHC patients despite lacking essential components for HCV viral replication. These short fragments were detected in 26 of 117 patients and were associated with significantly higher HCV RNA levels (P=0.018) and poor response to combination therapy (P=0.043). Moreover, the existence of HCV deletion mutants was significantly associated with virological relapse following combination therapy (P=0.046, OR=3.4).
Conclusions
HCV deletion mutants may affect the HCV life cycle and reduce the antiviral effects of interferon therapy for CHC.
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