Sequence analysis of NS3 protease gene in clinical strains of hepatitis C virus

S. Lodrini, S. Bagaglio, F. Canducci, M. S. De Mitri, P. Andreone, E. Loggi, A. Lazzarin, M. Clementi, G. Morsica

Research output: Contribution to journalArticle

Abstract

The amino terminal region of the non structural gene 3 (NS3) of hepatitis C virus (HCV) is a chymotripsin-like serine-protease responsible for cleavage of the non structural proteins of Hepatitis C virus (HCV). In order to investigate the genetic variation of this region, we developed a nested PCR to obtain NS3 protease sequences from 54 patients chronically infected with HCV genotypes 1a, 1b and 3, respectively. Comparison of nucleotide and amino acids sequences of NS3 protease domain with consensus sequence obtained within the same genotype, showed 3.73% nucleotide divergence and 1.64% amino acid divergence in isolates of genotype 3a, whereas isolates 1a exhibited 4.45% nucleotide and 4% amino acid change, respectively. Finally, NS3 sequence from 1b isolates revealed 6.47% nucleotide and 3.5 % aa changes. Comparison of consensus amino acid sequences derived from isolates 1a, 1b and 3, with the HCV prototypes showed a low amino acid sequence diversity. However, the consensus sequence of HCV genotype 3 isolates showed an amino acid changed from the prototype, that was located within a region important for enzyme structure and activity. These results indicated that the NS3 protease gene is highly conserved within the same HCV genotype. The domains involved in enzyme function were highly conserved in 1a and 1b strains, whereas consensus sequence of isolates 3a showed that the majority of these strains were not perfectly conserved in one of such regions. These findings altogether suggested that the NS3 protease enzyme of HCV may constitute an important target for antiviral therapy, but the NS3 protease variability of isolates 3 within a region that is a potential target for antiviral therapy could pose a problem for structure based drug development.

Original languageEnglish
Pages (from-to)198-204
Number of pages7
JournalJournal of Biological Regulators and Homeostatic Agents
Volume17
Issue number2
Publication statusPublished - Apr 2003

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Keywords

  • HCV
  • HCV genotype
  • NS3 protease

ASJC Scopus subject areas

  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Physiology (medical)
  • Medicine (miscellaneous)
  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

Lodrini, S., Bagaglio, S., Canducci, F., De Mitri, M. S., Andreone, P., Loggi, E., Lazzarin, A., Clementi, M., & Morsica, G. (2003). Sequence analysis of NS3 protease gene in clinical strains of hepatitis C virus. Journal of Biological Regulators and Homeostatic Agents, 17(2), 198-204.