scholarly journals Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection

Hepatology ◽  
1997 ◽  
Vol 25 (3) ◽  
pp. 745-749 ◽  
Author(s):  
K Chayama ◽  
A Tsubota ◽  
M Kobayashi ◽  
K Okamoto ◽  
M Hashimoto ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Virus Infection ◽  
Amino Acid Substitutions ◽  
Interferon Treatment ◽  
Hepatitis C Virus Infection ◽  
Virus Load ◽  
Genotype 1B ◽  
Multiple Amino Acid

Serological and salivary markers compared with biochemical markers for monitoring interferon treatment for hepatitis C virus infection

1995 ◽  
Vol 47 (4) ◽  
pp. 429-434 ◽  
Author(s):  
Kirsty M. Roy ◽  
Jeremy Bagg ◽  
George L. A. Bird ◽  
Elizabeth Spence ◽  
Edward A. Follett ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Biochemical Markers ◽  
Interferon Treatment ◽  
Hepatitis C Virus Infection

scholarly journals Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
María Eugenia Soria ◽  
Carlos García-Crespo ◽  
Brenda Martínez-González ◽  
Lucía Vázquez-Sirvent ◽  
Rebeca Lobo-Vega ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Treatment Failure ◽  
Antiviral Agents ◽  
Three Dimensional ◽  
Sustained Viral Response ◽  
Amino Acid Substitutions ◽  
Hepatitis C Virus Infection ◽  
Bona Fide

ABSTRACT Despite the high virological response rates achieved with current directly acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 2% to 5% of treated patients do not achieve a sustained viral response. The identification of amino acid substitutions associated with treatment failure requires analytical designs, such as subtype-specific ultradeep sequencing (UDS) methods, for HCV characterization and patient management. Using this procedure, we have identified six highly represented amino acid substitutions (HRSs) in NS5A and NS5B of HCV, which are not bona fide resistance-associated substitutions (RAS), from 220 patients who failed therapy. They were present frequently in basal and posttreatment virus of patients who failed different DAA-based therapies. Contrary to several RAS, HRSs belong to the acceptable subset of substitutions according to the PAM250 replacement matrix. Their mutant frequency, measured by the number of deep sequencing reads within the HCV quasispecies that encode the relevant substitutions, ranged between 90% and 100% in most cases. They also have limited predicted disruptive effects on the three-dimensional structures of the proteins harboring them. Possible mechanisms of HRS origin and dominance, as well as their potential predictive value for treatment response, are discussed.

HLA class II genotypes associated with chronic hepatitis C virus infection and response to alpha-interferon treatment in Poland

2000 ◽  
Vol 20 (3) ◽  
pp. 234-239 ◽  
Author(s):  
Marta Wawrzynowicz-Syczewska ◽  
James A. Underhill ◽  
Michael A. Clare ◽  
Anna Boron-Kaczmarska ◽  
Ian G. McFarlane ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Chronic Hepatitis C ◽  
Hla Class Ii ◽  
Alpha Interferon ◽  
Interferon Treatment ◽  
Hepatitis C Virus Infection ◽  
Chronic Hepatitis C Virus

Long-lasting remission of primary hepatic lymphoma and hepatitis C virus infection achieved by the alpha-interferon treatment

2004 ◽  
Vol 5 (6) ◽  
pp. 530-533 ◽  
Author(s):  
Emilio Iannitto ◽  
Emanuele Ammatuna ◽  
Claudio Tripodo ◽  
Carla Marino ◽  
Giuseppina Calvaruso ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Alpha Interferon ◽  
Interferon Treatment ◽  
Hepatitis C Virus Infection ◽  
Primary Hepatic Lymphoma

scholarly journals Interferon Resistance of Hepatitis C Virus Genotype 1b: Relationship to Nonstructural 5A Gene Quasispecies Mutations

1998 ◽  
Vol 72 (4) ◽  
pp. 2795-2805 ◽  
Author(s):  
Jean-Michel Pawlotsky ◽  
Georgios Germanidis ◽  
Avidan U. Neumann ◽  
Muriel Pellerin ◽  
Pierre-Olivier Frainais ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Critical Role ◽  
Patient Specific ◽  
Amino Acid Substitutions ◽  
Virus Genotype ◽  
Ns5a Protein ◽  
Genotype 1B

ABSTRACT A 40-amino-acid sequence located in the nonstructural 5A (NS5A) protein of hepatitis C virus genotype 1b (HCV-1b) was recently suggested to be the interferon sensitivity-determining region (ISDR), because HCV-1b strains with an ISDR amino acid sequence identical to that of the prototype strain HCV-J were found to be resistant to alpha interferon (IFN-α) whereas strains with amino acid substitutions were found to be sensitive (N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, N. Izumi, F. Marumo, and C. Sato, J. Clin. Invest. 96:224–230, 1995; N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, Y. Ogura, N. Izumi, F. Marumo, and C. Sato, N. Engl. J. Med. 334:77–81, 1996). We used single-strand conformation polymorphism (SSCP) analysis, combined with cloning and sequencing strategies, to characterize NS5A quasispecies in HCV-1b-infected patients and determine the relationships between pre- and posttreatment NS5A quasispecies mutations and the IFN-α sensitivity of HCV-1b. The serine residues involved in phosphorylation of NS5A protein were highly conserved both in the various patients and in quasispecies in a given patient, suggesting that phosphorylation is important in NS5A protein function. A hot spot for amino acid substitutions was found at positions 2217 to 2218; it could be the result of either strong selection pressure or tolerance to these amino acid replacements. The proportion of synonymous mutations was significantly higher than the proportion of nonsynonymous mutations, suggesting that genetic variability in the region studied was the result of high mutation rates and viral replication kinetics rather than of positive selection. Sustained HCV RNA clearance was associated with low viral load and low nucleotide sequence entropy, suggesting (i) that the replication kinetics when treatment is started plays a critical role in HCV-1b sensitivity to IFN-α and (ii) that HCV-1b resistance to IFN-α could be conferred by numerous and/or related mutations that could be patient specific and located at different positions throughout the viral genome and could allow escape variants to be selected by IFN-α-stimulated immune responses. No NS5A sequence appeared to be intrinsically resistant or sensitive to IFN-α, but the HCV-J sequence was significantly more frequent in nonresponder quasispecies than in sustained virological responder quasispecies, suggesting that the balance between NS5A quasispecies sequences in infected patients could have a subtle regulatory influence on HCV replication.

scholarly journals Interferon treatment for hepatitis C virus infection in patients on haemodialysis

1997 ◽  
Vol 12 (7) ◽  
pp. 1414-1419 ◽  
Author(s):  
T. M. Chan ◽  
P. C. Wu ◽  
J. Y. Lau ◽  
A. S. Lok ◽  
C. L. Lai ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Interferon Treatment ◽  
Hepatitis C Virus Infection
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