Molecular characterization of genotype 2 and 4 hepatitis C virus isolates in French blood donors

Abstract

The subtype distribution of 142 genotype 2 and 97 genotype 4 hepatitis C virus (HCV) isolates from the sera of 1,319 volunteer blood donors in France was determined by gene sequencing and by phylogenetic analysis of the NS5B region and E1 envelope. Findings underlined a wide range of subtypes in both genotypes, that is, 20 in HCV-2 and 11 in HCV-4. Eighteen of these 31 subtypes had not been defined previously. Some subtypes, that is, 2a, 2b, 2c, 2i, 2k, 4a, and 4d, showed numerous strains while subtypes in donors from West Africa or Central Africa showed an endemic profile with only a few strains. A Bayesian coalescence approach was used to estimate the demographic history of each HCV subtype. The estimated mean dates of the most recent common ancestors (MRCA) were 1,889 (confidence interval (CI), 1,842-1,930) for HCV-2a, 1,886 (CI, 1,843-1,921) for HCV-2b, 1,791 (CI, 1,699-1,848) for HCV-2c, 1,846 (CI, 1,803-1,878) for HCV-2i, 1,911 (CI, 1,879-1,937) for HCV-4a, and 1,957 (CI, 1,943-1,967) for HCV-4d. The period of spread for subtype 2b, 2c, and 2i was between 1900 and 1960 whereas rapid exponential spread for subtype 2a, 4a, and 4d occurred in the 1960s. The inferred histories of population growth indicated that transmission rates differed according to HCV subtype. These results may help to predict the future burden of HCV in France.

Colonial History and Contemporary Transmission Shape the Genetic Diversity of Hepatitis C Virus Genotype 2 in Amsterdam

“…During the 20th century, transmission via contaminated blood, blood products, invasive procedures, and IDU eventually resulted in the global dispersal of HCV-2, particularly subtypes 2a and 2b, which cause the vast majority of HCV-2 infections in developed countries (9,11,44). Interestingly, two recent studies from France revealed a wide variety of HCV-2 subtypes, including among the native French population (5,40).…”

Predominance of hepatitis C virus genotype 4 infection and rapid transmission between 1935 and 1965 in the Central African Republic

“…The MRCAs of HCV-4 in CAR and Cameroon are much older than that of the genotype 4 strains found in Europe (MRCA, approx. 1900) (Cantaloube et al, 2008) and Egypt (MRCA existed approx. 100 years ago) (Pybus et al, 2003;Tanaka et al, 2004), reinforcing our previous suggestion that HCV-4 originated in central Africa, diverged and then spread to the rest of the world.…”

The Cobas AmpliPrep-Cobas TaqMan real-time polymerase chain reaction assay fails to detect hepatitis C virus RNA in highly viremic genotype 4 clinical samples

“…4 Modeling suggests that HCV genotype 4 could play an important role in the future HCV burden in industrialized countries. 5 Further studies are warranted to assess the frequency of undetected HCV RNA with the CAP-CTM assay. Improvement in this assay is now urgently needed in order to ensure accurate quantification of HCV RNA, regardless of the HCV genotype, for optimal use in clinical trials and practice.…”