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Fluctuations of hepatitis C virus load are not related to amino acid substitutions in hypervariable region 1 and interferon sensitivity determining region
Author(s) -
Hashimoto Michie,
Chayama Kazuaki,
Kobayashi Masahiro,
Tsubota Akihito,
Arase Yasuji,
Saitoh Satoshi,
Suzuki Yoshiyuki,
Ikeda Kenji,
Matsuda Marie,
Koike Hiromi,
Kobayashi Mariko,
Handa Hiroshi,
Kumada Hiromitsu
Publication year - 1999
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/(sici)1096-9071(199907)58:3<247::aid-jmv10>3.0.co;2-3
Subject(s) - hypervariable region , viremia , titer , virology , viral load , virus , interferon , biology , amino acid , hepatitis c virus , antibody , genetics
Hepatitis C virus (HCV) load is one of the most important predictive factors of response to interferon treatment. However, little is known about the mode and determinants of viremia. The mode of viremia was investigated in 78 patients with chronic HCV genotype 1b infection during 1–2 years follow up. Virus load, determined by a branched chain DNA amplification assay, was stable in 73 of 78 (93.6%) patients, whereas 5 (6.4%) showed marked fluctuation (from undetectable level to more than 10 Meq/ml) in viral titer. To study the mechanisms mediating fluctuations in viral titer, amino acid sequences of two regions were examined; hypervariable region (HVR) 1 and the interferon sensitivity determining region (ISDR). Multiple amino acid substitutions were observed in HVR 1 but no relationship was evident between substitutions and virus titers. In contrast, no amino acid substitutions were observed in the ISDR in any patients with stable virus titer during a follow‐up period of 12–24 months (7–24 samples) or in one patient who was observed for 15 years. Interestingly, multiple amino acid substitutions in the ISDR appeared in only two of the five patients with marked titer fluctuation, when the virus decreased markedly. Alanine aminotransferase levels in these five patients correlated with viral load. The data suggest that amino acid substitutions in HVR1 and ISDR are not essential for changes in viral titer. Possible mechanisms of fluctuations of viral titer and amino acid substitutions in the ISDR accompanying marked reductions in viral load are discussed. J. Med. Virol. 58:247–255, 1999. © 1999 Wiley‐Liss, Inc.