Molecular heterogeneity and new subtypes of HCV genotype 4.

The subtype distribution of HCV genotype 4 was studied in two different African countries, Egypt and Tanzania. The HCV isolates were obtained from epidemiological studies involving, respectively, 135 hepatopatic patients and 1043 pregnant women and outpatients. Sequence comparison and phylogenetic analysis of the NS5b genome region (nt 8327-8499) were performed. Fourteen out of 18 isolates from Egypt, but only 3 out of 6 isolates from Tanzania clustered in the same branch of subtype 4a. Three new proposed subtypes have been identified. The first includes 1 isolate from Egypt (EGY15); the second, 2 isolates from Egypt (EGY193 and EGY44) and 2 isolates from Tanzania (D776, D61); and the third, 1 isolate from Egypt (EGY47) and 1 isolate from Tanzania (D70). These isolates cluster in branches different from any other, corresponding to a known subtype of genotype 4. In conclusion, remarkable genetic heterogeneity has been found among genotype 4 isolates simultaneously circulating in a restricted area. This was particularly observed in the study performed in Tanzania. Potential concern about the sensitivity of diagnostic assays and possible implications in the development of future vaccines have been stressed.