Tags

Type your tag names separated by a space and hit enter

Sequence analysis of NS3 protease gene in clinical strains of hepatitis C virus.
J Biol Regul Homeost Agents. 2003 Apr-Jun; 17(2):198-204.JB

Abstract

The amino terminal region of the non structural gene 3 (NS3) of hepatitis C virus (HCV) is a chymotripsinlike 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.

Authors+Show Affiliations

Division of Infectious Diseases, San Raffaele Vita-Salute University, San Raffaele Scientific Institute IRCCS, Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14518724

Citation

Lodrini, S, et al. "Sequence Analysis of NS3 Protease Gene in Clinical Strains of Hepatitis C Virus." Journal of Biological Regulators and Homeostatic Agents, vol. 17, no. 2, 2003, pp. 198-204.
Lodrini S, Bagaglio S, Canducci F, et al. Sequence analysis of NS3 protease gene in clinical strains of hepatitis C virus. J Biol Regul Homeost Agents. 2003;17(2):198-204.
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.
Lodrini S, et al. Sequence Analysis of NS3 Protease Gene in Clinical Strains of Hepatitis C Virus. J Biol Regul Homeost Agents. 2003 Apr-Jun;17(2):198-204. PubMed PMID: 14518724.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequence analysis of NS3 protease gene in clinical strains of hepatitis C virus. AU - Lodrini,S, AU - Bagaglio,S, AU - Canducci,F, AU - De Mitri,M S, AU - Andreone,P, AU - Loggi,E, AU - Lazzarin,A, AU - Clementi,M, AU - Morsica,G, PY - 2003/10/2/pubmed PY - 2004/6/21/medline PY - 2003/10/2/entrez SP - 198 EP - 204 JF - Journal of biological regulators and homeostatic agents JO - J Biol Regul Homeost Agents VL - 17 IS - 2 N2 - The amino terminal region of the non structural gene 3 (NS3) of hepatitis C virus (HCV) is a chymotripsinlike 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. SN - 0393-974X UR - https://www.unboundmedicine.com/medline/citation/14518724/Sequence_analysis_of_NS3_protease_gene_in_clinical_strains_of_hepatitis_C_virus_ L2 - https://www.diseaseinfosearch.org/result/3332 DB - PRIME DP - Unbound Medicine ER -