Abstract
Hepatitis C virus (HCV)-positive sera from 106 chronically infected patients which had previously been genotyped were characterized by serotyping. Genotypes were determined by a first-generation line probe assay (INNO-LiPA HCV) and by sequence analyses of the core, core-E1, and NS5B regions. HCV serotypes were determined by measuring type-specific antibodies to NS4-derived peptide antigens (Murex HCV serotyping 1-6 assay). Of 106 serum samples, serotype-specific antibodies were detected in 88 (sensitivity, 83.0%), and 77 (specificity, 87.5%) of these serotypeable samples revealed a corresponding serotype (total concordance, 72.6%). Eleven samples revealed discrepant results as follows. (i) Five serum samples in which only a single genotype was detected contained an additional serotype. (ii) In one sample with two genotypes only one serotype was detected. (iii) In five isolates the serotype (all serotype 1) was completely different from the genotype. Double infections, as determined by genotyping, were confirmed by serotyping in two of four cases. Of 11 serum samples from chronically infected hemodialysis patients, 7 (64%) were reactive in the serotyping assay. In conclusion, genotyping allows discrimination between (sub)types but requires the relatively complex reverse transcriptase PCR. The novel serotyping assay offers an alternative method to distinguish the major types of HCV, although the sensitivity of the assay may be limited by the immunocompetence of the infected host.
Full Text
The Full Text of this article is available as a PDF (193.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bhattacherjee V., Prescott L. E., Pike I., Rodgers B., Bell H., El-Zayadi A. R., Kew M. C., Conradie J., Lin C. K., Marsden H. Use of NS-4 peptides to identify type-specific antibody to hepatitis C virus genotypes 1, 2, 3, 4, 5 and 6. J Gen Virol. 1995 Jul;76(Pt 7):1737–1748. doi: 10.1099/0022-1317-76-7-1737. [DOI] [PubMed] [Google Scholar]
- Bukh J., Wantzin P., Krogsgaard K., Knudsen F., Purcell R. H., Miller R. H. High prevalence of hepatitis C virus (HCV) RNA in dialysis patients: failure of commercially available antibody tests to identify a significant number of patients with HCV infection. Copenhagen Dialysis HCV Study Group. J Infect Dis. 1993 Dec;168(6):1343–1348. doi: 10.1093/infdis/168.6.1343. [DOI] [PubMed] [Google Scholar]
- Chan S. W., Simmonds P., McOmish F., Yap P. L., Mitchell R., Dow B., Follett E. Serological responses to infection with three different types of hepatitis C virus. Lancet. 1991 Nov 30;338(8779):1391–1391. doi: 10.1016/0140-6736(91)92265-4. [DOI] [PubMed] [Google Scholar]
- Chemello L., Cavalletto D., Pontisso P., Bortolotti F., Donada C., Donadon V., Frezza M., Casarin P., Alberti A. Patterns of antibodies to hepatitis C virus in patients with chronic non-A, non-B hepatitis and their relationship to viral replication and liver disease. Hepatology. 1993 Feb;17(2):179–182. [PubMed] [Google Scholar]
- Dusheiko G., Schmilovitz-Weiss H., Brown D., McOmish F., Yap P. L., Sherlock S., McIntyre N., Simmonds P. Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease. Hepatology. 1994 Jan;19(1):13–18. [PubMed] [Google Scholar]
- Féray C., Gigou M., Samuel D., Paradis V., Mishiro S., Maertens G., Reynés M., Okamoto H., Bismuth H., Bréchot C. Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation. Gastroenterology. 1995 Apr;108(4):1088–1096. doi: 10.1016/0016-5085(95)90207-4. [DOI] [PubMed] [Google Scholar]
- Lau J. Y., Simmonds P., Urdea M. S. Implications of variations of "conserved" regions of hepatitis C virus genome. Lancet. 1995 Aug 12;346(8972):425–426. doi: 10.1016/s0140-6736(95)92786-7. [DOI] [PubMed] [Google Scholar]
- Machida A., Ohnuma H., Tsuda F., Munekata E., Tanaka T., Akahane Y., Okamoto H., Mishiro S. Two distinct subtypes of hepatitis C virus defined by antibodies directed to the putative core protein. Hepatology. 1992 Oct;16(4):886–891. doi: 10.1002/hep.1840160406. [DOI] [PubMed] [Google Scholar]
- McOmish F., Chan S. W., Dow B. C., Gillon J., Frame W. D., Crawford R. J., Yap P. L., Follett E. A., Simmonds P. Detection of three types of hepatitis C virus in blood donors: investigation of type-specific differences in serologic reactivity and rate of alanine aminotransferase abnormalities. Transfusion. 1993 Jan;33(1):7–13. doi: 10.1046/j.1537-2995.1993.33193142314.x. [DOI] [PubMed] [Google Scholar]
- McOmish F., Yap P. L., Dow B. C., Follett E. A., Seed C., Keller A. J., Cobain T. J., Krusius T., Kolho E., Naukkarinen R. Geographical distribution of hepatitis C virus genotypes in blood donors: an international collaborative survey. J Clin Microbiol. 1994 Apr;32(4):884–892. doi: 10.1128/jcm.32.4.884-892.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Medin C., Allander T., Roll M., Jacobson S. H., Grillner L. Seroconversion to hepatitis C virus in dialysis patients: a retrospective and prospective study. Nephron. 1993;65(1):40–45. doi: 10.1159/000187438. [DOI] [PubMed] [Google Scholar]
- Mondelli M. U., Cerino A., Bono F., Cividini A., Maccabruni A., Aricò M., Malfitano A., Barbarini G., Piazza V., Minoli L. Hepatitis C virus (HCV) core serotypes in chronic HCV infection. J Clin Microbiol. 1994 Oct;32(10):2523–2527. doi: 10.1128/jcm.32.10.2523-2527.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nagayama R., Tsuda F., Okamoto H., Wang Y., Mitsui T., Tanaka T., Miyakawa Y., Mayumi M. Genotype dependence of hepatitis C virus antibodies detectable by the first-generation enzyme-linked immunosorbent assay with C100-3 protein. J Clin Invest. 1993 Sep;92(3):1529–1533. doi: 10.1172/JCI116731. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okamoto H., Sugiyama Y., Okada S., Kurai K., Akahane Y., Sugai Y., Tanaka T., Sato K., Tsuda F., Miyakawa Y. Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources. J Gen Virol. 1992 Mar;73(Pt 3):673–679. doi: 10.1099/0022-1317-73-3-673. [DOI] [PubMed] [Google Scholar]
- Oliva J. A., Maymo R. M., Carrio J., Delgado O., Mallafre J. M. Late seroconversion of C virus markers in hemodialysis patients. Kidney Int Suppl. 1993 Jun;41:S153–S156. [PubMed] [Google Scholar]
- Orito E., Mizokami M., Mizoguchi N., Ohba K., Tohnai M., Yamanaka H., Oguri T., Hirashima N., Koide T., Kano H. Hepatitis C virus serotype II responds more favorably to interferon-alpha therapy. J Hepatol. 1994 Jul;21(1):130–132. doi: 10.1016/s0168-8278(94)80149-5. [DOI] [PubMed] [Google Scholar]
- Pawlotsky J. M., Tsakiris L., Roudot-Thoraval F., Pellet C., Stuyver L., Duval J., Dhumeaux D. Relationship between hepatitis C virus genotypes and sources of infection in patients with chronic hepatitis C. J Infect Dis. 1995 Jun;171(6):1607–1610. doi: 10.1093/infdis/171.6.1607. [DOI] [PubMed] [Google Scholar]
- Pontisso P., Gerotto M., Chemello L., Casarin C., Tisminetzky S., Baralle F., Alberti A. Hepatitis C virus genotypes HCV-1a and HCV-1b: the clinical point of view. J Infect Dis. 1995 Mar;171(3):760–760. [PubMed] [Google Scholar]
- Pozzato G., Kaneko S., Moretti M., Crocè L. S., Franzin F., Unoura M., Bercich L., Tiribelli C., Crovatto M., Santini G. Different genotypes of hepatitis C virus are associated with different severity of chronic liver disease. J Med Virol. 1994 Jul;43(3):291–296. doi: 10.1002/jmv.1890430318. [DOI] [PubMed] [Google Scholar]
- Pozzato G., Moretti M., Franzin F., Crocè L. S., Tiribelli C., Masayu T., Kaneko S., Unoura M., Kobayashi K. Severity of liver disease with different hepatitis C viral clones. Lancet. 1991 Aug 24;338(8765):509–509. doi: 10.1016/0140-6736(91)90578-d. [DOI] [PubMed] [Google Scholar]
- Qu D., Li J. S., Vitvitski L., Mechai S., Berby F., Tong S. P., Bailly F., Wang Q. S., Martin J. L., Trépo C. Hepatitis C virus genotypes in France: comparison of clinical features of patients infected with HCV type I and type II. J Hepatol. 1994 Jul;21(1):70–75. doi: 10.1016/s0168-8278(94)80139-8. [DOI] [PubMed] [Google Scholar]
- Silini E., Bono F., Cividini A., Cerino A., Bruno S., Rossi S., Belloni G., Brugnetti B., Civardi E., Salvaneschi L. Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities. Hepatology. 1995 Feb;21(2):285–290. [PubMed] [Google Scholar]
- Simmonds P., Alberti A., Alter H. J., Bonino F., Bradley D. W., Brechot C., Brouwer J. T., Chan S. W., Chayama K., Chen D. S. A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology. 1994 May;19(5):1321–1324. [PubMed] [Google Scholar]
- Simmonds P., Rose K. A., Graham S., Chan S. W., McOmish F., Dow B. C., Follett E. A., Yap P. L., Marsden H. Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV): use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3. J Clin Microbiol. 1993 Jun;31(6):1493–1503. doi: 10.1128/jcm.31.6.1493-1503.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simmonds P. Variability of hepatitis C virus. Hepatology. 1995 Feb;21(2):570–583. doi: 10.1002/hep.1840210243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stuyver L., Rossau R., Wyseur A., Duhamel M., Vanderborght B., Van Heuverswyn H., Maertens G. Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol. 1993 Jun;74(Pt 6):1093–1102. doi: 10.1099/0022-1317-74-6-1093. [DOI] [PubMed] [Google Scholar]
- Stuyver L., Van Arnhem W., Wyseur A., DeLeys R., Maertens G. Analysis of the putative E1 envelope and NS4a epitope regions of HCV type 3. Biochem Biophys Res Commun. 1993 Apr 30;192(2):635–641. doi: 10.1006/bbrc.1993.1462. [DOI] [PubMed] [Google Scholar]
- Stuyver L., Wyseur A., van Arnhem W., Lunel F., Laurent-Puig P., Pawlotsky J. M., Kleter B., Bassit L., Nkengasong J., van Doorn L. J. Hepatitis C virus genotyping by means of 5'-UR/core line probe assays and molecular analysis of untypeable samples. Virus Res. 1995 Oct;38(2-3):137–157. doi: 10.1016/0168-1702(95)00052-r. [DOI] [PubMed] [Google Scholar]
- Tanaka E., Kiyosawa K., Matsumoto A., Sodeyama T., Urushihara A., Suzuki T., Kobayashi M., Furuta S. Prevalence of hepatitis C virus with different genotypes determined by a group-specific antibody assay in Japanese patients with chronic liver diseases due to hepatitis C virus infection. Jpn J Med Sci Biol. 1994 Feb;47(1):47–57. doi: 10.7883/yoken1952.47.47. [DOI] [PubMed] [Google Scholar]
- Tanaka T., Tsukiyama-Kohara K., Yamaguchi K., Yagi S., Tanaka S., Hasegawa A., Ohta Y., Hattori N., Kohara M. Significance of specific antibody assay for genotyping of hepatitis C virus. Hepatology. 1994 Jun;19(6):1347–1353. [PubMed] [Google Scholar]
- Tsubota A., Chayama K., Ikeda K., Yasuji A., Koida I., Saitoh S., Hashimoto M., Iwasaki S., Kobayashi M., Hiromitsu K. Factors predictive of response to interferon-alpha therapy in hepatitis C virus infection. Hepatology. 1994 May;19(5):1088–1094. [PubMed] [Google Scholar]
- Tsukiyama-Kohara K., Yamaguchi K., Maki N., Ohta Y., Miki K., Mizokami M., Ohba K., Tanaka S., Hattori N., Nomoto A. Antigenicities of Group I and II hepatitis C virus polypeptides--molecular basis of diagnosis. Virology. 1993 Feb;192(2):430–437. doi: 10.1006/viro.1993.1058. [DOI] [PubMed] [Google Scholar]
- Yuki N., Hayashi N., Hagiwara H., Takehara T., Katayama K., Kasahara A., Fusamoto H., Kamada T. Quantitative analysis of antibodies to hepatitis C virus during interferon-alpha therapy. Hepatology. 1993 Jun;17(6):960–965. [PubMed] [Google Scholar]
- Zaaijer H. L., Cuypers H. T., Reesink H. W., Winkel I. N., Gerken G., Lelie P. N. Reliability of polymerase chain reaction for detection of hepatitis C virus. Lancet. 1993 Mar 20;341(8847):722–724. doi: 10.1016/0140-6736(93)90488-3. [DOI] [PubMed] [Google Scholar]
- van Doorn L. J., Kleter B., Stuyver L., Maertens G., Brouwer H., Schalm S., Heijtink R., Quint W. Analysis of hepatitis C virus genotypes by a line probe assay and correlation with antibody profiles. J Hepatol. 1994 Jul;21(1):122–129. doi: 10.1016/s0168-8278(94)80148-7. [DOI] [PubMed] [Google Scholar]
- van Doorn L. J., Kleter G. E., Stuyver L., Maertens G., Brouwer J. T., Schalm S. W., Heijtink R. A., Quint W. G. Sequence analysis of hepatitis C virus genotypes 1 to 5 reveals multiple novel subtypes in the Benelux countries. J Gen Virol. 1995 Jul;76(Pt 7):1871–1876. doi: 10.1099/0022-1317-76-7-1871. [DOI] [PubMed] [Google Scholar]