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Complete nucleotide sequence of genotype 4 hepatitis C viruses isolated from patients co-infected with human immunodeficiency virus type 1.
Virus Res. 2007 Feb; 123(2):161-9.VR

Abstract

The hepatitis C virus (HCV) genotype 4 is spreading among southern European intravenous drug users, who are frequently co-infected with human immunodeficiency virus type 1 (HIV-1). Response to interferon (IFN) alpha-based therapies in HIV-1 positive patients co-infected with HCV genotype 4 is poor, similar to that obtained for HCV genotype 1 and much lower than for HCV genotypes 2 and 3. The lack of sequence data related to HCV of genotype 4 prompted us to sequence the complete genome of two genotype 4 variants isolated from two HIV-1 co-infected patients (24 and 25). Our aim was to investigate the evolutionary relationships of the former variants with other genotypes and/or genotype 4 subtypes. Sequence alignments and phylogenetic analysis from genomic regions 5'NC, core-E1 and NS5B revealed that the variants isolated from patients 24 and 25 (both subtyped 4c/4d by INNO-LIPA II HCV) belong to subtypes 4d and 4a, respectively. When looking at the complete genome sequence one of the variants showed a new genotype 4 subtype. Interestingly, sequence length differences in the interferon sensitivity determining region coding regions were observed when compared with sequences from other genotypes. Similarly, when the catalytic efficiency of the NS3/4 protease from patients 24 and 25 samples were determined, they displayed 70.6+/-7.7 and 23.5+/-3.4%, respectively, of the activity shown by genotype 1 NS3/4 proteases. Overall, pairwise comparison and phylogenetic analysis of nucleotide sequences of the complete genome or the different protein-encoding regions showed that genotype 4 sequences were more closely related to genotype 1 sequences. The description of new HCV genome variants may help our understanding of the HCV biology as well as the role of different genotypes in HCV treatment and therapy response.

Authors+Show Affiliations

Fundació irsiCaixa, Universitat Autònoma de Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17023084

Citation

Franco, Sandra, et al. "Complete Nucleotide Sequence of Genotype 4 Hepatitis C Viruses Isolated From Patients Co-infected With Human Immunodeficiency Virus Type 1." Virus Research, vol. 123, no. 2, 2007, pp. 161-9.
Franco S, Tural C, Clotet B, et al. Complete nucleotide sequence of genotype 4 hepatitis C viruses isolated from patients co-infected with human immunodeficiency virus type 1. Virus Res. 2007;123(2):161-9.
Franco, S., Tural, C., Clotet, B., & Martínez, M. A. (2007). Complete nucleotide sequence of genotype 4 hepatitis C viruses isolated from patients co-infected with human immunodeficiency virus type 1. Virus Research, 123(2), 161-9.
Franco S, et al. Complete Nucleotide Sequence of Genotype 4 Hepatitis C Viruses Isolated From Patients Co-infected With Human Immunodeficiency Virus Type 1. Virus Res. 2007;123(2):161-9. PubMed PMID: 17023084.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complete nucleotide sequence of genotype 4 hepatitis C viruses isolated from patients co-infected with human immunodeficiency virus type 1. AU - Franco,Sandra, AU - Tural,Cristina, AU - Clotet,Bonaventura, AU - Martínez,Miguel Angel, Y1 - 2006/10/04/ PY - 2006/07/10/received PY - 2006/08/31/revised PY - 2006/09/01/accepted PY - 2006/10/7/pubmed PY - 2007/3/16/medline PY - 2006/10/7/entrez SP - 161 EP - 9 JF - Virus research JO - Virus Res VL - 123 IS - 2 N2 - The hepatitis C virus (HCV) genotype 4 is spreading among southern European intravenous drug users, who are frequently co-infected with human immunodeficiency virus type 1 (HIV-1). Response to interferon (IFN) alpha-based therapies in HIV-1 positive patients co-infected with HCV genotype 4 is poor, similar to that obtained for HCV genotype 1 and much lower than for HCV genotypes 2 and 3. The lack of sequence data related to HCV of genotype 4 prompted us to sequence the complete genome of two genotype 4 variants isolated from two HIV-1 co-infected patients (24 and 25). Our aim was to investigate the evolutionary relationships of the former variants with other genotypes and/or genotype 4 subtypes. Sequence alignments and phylogenetic analysis from genomic regions 5'NC, core-E1 and NS5B revealed that the variants isolated from patients 24 and 25 (both subtyped 4c/4d by INNO-LIPA II HCV) belong to subtypes 4d and 4a, respectively. When looking at the complete genome sequence one of the variants showed a new genotype 4 subtype. Interestingly, sequence length differences in the interferon sensitivity determining region coding regions were observed when compared with sequences from other genotypes. Similarly, when the catalytic efficiency of the NS3/4 protease from patients 24 and 25 samples were determined, they displayed 70.6+/-7.7 and 23.5+/-3.4%, respectively, of the activity shown by genotype 1 NS3/4 proteases. Overall, pairwise comparison and phylogenetic analysis of nucleotide sequences of the complete genome or the different protein-encoding regions showed that genotype 4 sequences were more closely related to genotype 1 sequences. The description of new HCV genome variants may help our understanding of the HCV biology as well as the role of different genotypes in HCV treatment and therapy response. SN - 0168-1702 UR - https://www.unboundmedicine.com/medline/citation/17023084/Complete_nucleotide_sequence_of_genotype_4_hepatitis_C_viruses_isolated_from_patients_co_infected_with_human_immunodeficiency_virus_type_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-1702(06)00265-6 DB - PRIME DP - Unbound Medicine ER -