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Mutations in NS5A region of hepatitis C virus genome correlate with presence of NS5A antibodies and response to interferon therapy for most common european hepatitis C virus genotypes
- Source :
- Hepatology, Hepatology, Wiley-Blackwell, 1998, 28 (6), pp.1674-1679. ⟨10.1002/hep.510280630⟩
- Publication Year :
- 1998
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1998.
-
Abstract
- International audience; A part of the hepatitis C virus (HCV) nonstructural protein 5A (NS5A) amino acid sequence, designated as an interferon (IFN)-sensitive determining region (ISDR), has been shown to be correlated with a response to IFN in Japanese patients. We have shown previously that the presence of NS5A antibodies (Abs) detected by the INNOLIA test (IL-NS5A Ab) is also correlated with a response to IFN. The aim of this study was to investigate, in a wide range of patients, the possible relationship within the NS5A protein between the sequence of ISDR and that used in the INNOLIA test designated as IL3R. Serum samples from 52 patients infected by HCV genotypes 1, 2, and 3 were analyzed before and after treatment. The patients were classified as nonresponders (NRs), responder-relapsers (RRs), or long-term responders (LTRs). We amplified the NS5A region for 42 patients using polymerase chain reaction (PCR), and these amplicons were sequenced directly. The 10 remaining patients were analyzed using PCR with mutation-specific primers. No correlation was found between the IL3R sequence of the HCV strains and the presence of the IL-NS5A Ab for all genotypes. However, for the subtype 1b, only 2 of 11 NR patients tested had an arginin in position 2218 within the ISDR versus 3 of 3 LTR and 10 of 13 RR patients. All patients with R-2218 had IL-NS5A Ab. For the genotype 1a, 2 of 2 LTR and 1 of 3 RR were mutated in position 2216-2218 in comparison to three NR sequences. For the genotype 3, no mutations were found in the region homologous to 1b-ISDR, but 4 of 5 LTR and RR patients had a mutation T-2161 to A or V versus 0 of 3 NR patients. A close correlation was found between arginin in position 2218 in ISDR, the presence of IL-NS5A Ab, and the response to IFN therapy for genotype 1b, but this association did not predict a long-term response. For genotype 3, a potential ISD mutation could be located at the codon 2161.
- Subjects :
- viruses
Hepacivirus
Drug Resistance
MESH: Amino Acid Sequence
Viral Nonstructural Proteins
medicine.disease_cause
Polymerase Chain Reaction
MESH: Genotype
0302 clinical medicine
Interferon
Genotype
MESH: Hepacivirus
0303 health sciences
biology
Hepatitis C
3. Good health
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
MESH: Drug Resistance
030211 gastroenterology & hepatology
MESH: Genome, Viral
MESH: Interferon-alpha
Antibody
medicine.drug
MESH: Antiviral Agents
MESH: Mutation
Hepatitis C virus
Molecular Sequence Data
Genome, Viral
Antiviral Agents
Antibodies
Virus
03 medical and health sciences
Flaviviridae
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
medicine
Humans
Amino Acid Sequence
NS5A
030304 developmental biology
MESH: Hepatitis C
MESH: Molecular Sequence Data
MESH: Humans
Hepatology
MESH: Antibodies
Interferon-alpha
MESH: Polymerase Chain Reaction
biology.organism_classification
Virology
Mutation
biology.protein
MESH: Viral Nonstructural Proteins
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Subjects
Details
- ISSN :
- 15273350 and 02709139
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Hepatology
- Accession number :
- edsair.doi.dedup.....ae0876af6fcb38fecbb18503add5e15f