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Analysis of hepatitis C virus quasispecies populations by temperature gradient gel electrophoresis

¹ Institut für Virologie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen
and² Städtisches Krankenhaus St George, 2. Klinik Innere Medizin, Delitzscher Strasse 141, 04129 Leipzig, Germany

Hepatitis C virus (HCV) forms complex quasispecies populations which consist of a large number of closely related genetic variants. This genetic heterogeneity may cause antigenic variation or drug resistance. We used heteroduplex analysis by temperature gradient gel electrophoresis (TGGE) to characterize genetic variants of HCV. The high resolution of TGGE was proven by comparison of DNA sequence data of different cDNA clones from the HCV 5'NCR with their corresponding migration pattern in TGGE. Using this method we were able to identify virus variants of the HCV 5'NCR even if they only differed from each other by a single base. HCV populations from three patients with chronic hepatitis C were found to consist of genetic variants, although the degree of the heterogeneity varied. In addition, we compared the genetic heterogeneity of the core and E2 regions of the HCV genome in one patient. Our results demonstrate that TGGE is a useful tool for characterization of the genetic heterogeneity of virus populations in vivo.

^* Author for correspondence. Fax +49 201 723 5929.

Received 15 August 1994; accepted 8 November 1994.

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