Genetic variability of German hepatitis C virus isolates.

Heterogeneity of hepatitis C viral (HCV) genomes of several isolates from different countries has been reported, but there is little information on HCV isolates for the Federal Republic of Germany. Therefore, the nucleotide (nt) and deduced amino acid (aa) sequences of interesting parts of the viral genome derived from different human isolates in Germany were compared with each other and with the nt and predicted aa sequences of recently published isolates. HCV sequences were obtained by reverse transcription of viral RNA extracted from serum followed by polymerase chain reaction (PCR) amplification. Within the 5' nontranslated region we found only 3 single nucleotide exchanges among 2 of our isolates, and in comparison to sequences of Japanese isolates 2 to 3 exchanges, and to U.S. isolates 1 to 5 exchanges (homologies 98% to > 99%). Determination of a 249-bp core sequence from two German isolates exhibited 3% sequence divergence. The sequence of the core region (nt 342-911) showed a homology of about 88-91% on nt level and 96-97% on aa level as compared to U.S. isolates and other German isolates, and a homology of 95-96% (nt) and 96-98% (aa), respectively, to Japanese isolates. Less homologies were noticed for the E1 and E2/NS1 genes, especially in the N-terminal E2/NS1 hypervariable domain. Our isolates HD1 and HD2 showed nt sequence homologies of about 72-81% and aa homologies of 76-88% to U.S., German, and French isolates, and 89-91% (nt) and 88-96% (aa), respectively, to Japanese isolates. These results indicate that various German isolates are more closely related to Japanese isolates and differ from other European isolates as reported so far. Because of a nucleotide sequence heterogeneity of up to 10% among the tested isolates, we conclude that more than one closely related but distinct viral genotype of HCV exists in Germany. Furthermore, heterogeneous sequences of HCV can be detected in a single patient suggesting multiple infection with different genomic variants or, alternatively, a genetic drift forced by mutational events as a consequence of host immune selection.