Variation analysis of E1 and E2 in HCV subtypes

Variation analysis of E1 and E2 in HCV subtypes Pegylated interferon and ribavirin combination therapy effectively suppresses viral replication in 50 %–60 % of hepatitis C virus (HCV)-infected patients. However, HCV-infected patients often display varied responses to therapy, and strains of subtype lb (the most widespread HCV subtype worldwide) have more-severe clinical manifestations, greater viral loads, and poorer responses to interferon treatment. Therefore, understanding the genomic variability of HCV is crucial to treatment of HCV infection. In this study, we used the appropriate software to analyze the nucleotide, and amino acid sequences of the envelope proteins (E1 and E2) of HCV to investigate the extent of their variability in several HCV subtypes (1a, 1b, 2a, 2b, 3a, 4a, 5a and 6a) and calculated the ratio of nonsynonymous to synonymous substitutions (dN/dS) in these proteins to investigate the immunological pressure acting on them. We also predicted the N-glycosylation sites in E1 and E2 to determine their association with viral neutralization. We found that E1 is more variable, has a higher dN/dS ratio, and has more N-glycosylation sites than E2 in HCV subtype 1b. This indicates that the variability of E1, its dN/dS ratio, and its degree of N-glycosylation might play an important role in the treatment of infection with HCV subtype 1b. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Variation analysis of E1 and E2 in HCV subtypes

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Publisher
Springer Journals
Copyright
Copyright © 2015 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2533-9
Publisher site
See Article on Publisher Site

Abstract

Pegylated interferon and ribavirin combination therapy effectively suppresses viral replication in 50 %–60 % of hepatitis C virus (HCV)-infected patients. However, HCV-infected patients often display varied responses to therapy, and strains of subtype lb (the most widespread HCV subtype worldwide) have more-severe clinical manifestations, greater viral loads, and poorer responses to interferon treatment. Therefore, understanding the genomic variability of HCV is crucial to treatment of HCV infection. In this study, we used the appropriate software to analyze the nucleotide, and amino acid sequences of the envelope proteins (E1 and E2) of HCV to investigate the extent of their variability in several HCV subtypes (1a, 1b, 2a, 2b, 3a, 4a, 5a and 6a) and calculated the ratio of nonsynonymous to synonymous substitutions (dN/dS) in these proteins to investigate the immunological pressure acting on them. We also predicted the N-glycosylation sites in E1 and E2 to determine their association with viral neutralization. We found that E1 is more variable, has a higher dN/dS ratio, and has more N-glycosylation sites than E2 in HCV subtype 1b. This indicates that the variability of E1, its dN/dS ratio, and its degree of N-glycosylation might play an important role in the treatment of infection with HCV subtype 1b.

Journal

Archives of VirologySpringer Journals

Published: Oct 1, 2015

References

  • Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes
    Simmonds, P; Bukh, J
  • Higher dN/dS ratios in the HCV core gene, but not in the E1/HVR1 gene, are associated with human immunodeficiency virus-associated immunosuppression
    Xu, CH; Shen, T

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