Back to the origin of HCV 2c subtype and spreading to the Calabria region (Southern Italy) over the last two centuries: a phylogenetic study.

Circulation of HCV genotype 2 has been described in European Countries where numerous subtypes and unclassified HCV 2 lineages have been reported. In Italy, subtype 1b is the most prevalent, followed by genotype 2. In the present study, phylogeny of HCV 2c was investigated. The phylogeny of HCV 2c isolated from 54 Italian patients in the Calabria region (Southern Italy) was investigated by analyzing a fragment of the NS5B gene. Patients came from 5 metropolitan areas and a small village (Sersale). These areas were geographically dispersed throughout the entire region. A Bayesian coalescent-based framework was used to estimate origin and spreading of HCV 2c in this region. Phylogenetic analysis showed that 28 Italian sequences were intermixed with foreign HCV 2c reference sequences and grouped into 3 major clades: A, B, and C. Nineteen inter-clade sequences were associated uniquely with surgery as risk factor for HCV acquisition. By contrast, a sub-cluster within clade B was associated with blood transfusion. Moreover, sequences from Sersale village grouped in the Italian sub-cluster and were intermixed with 10 sequences from metropolitan areas. The three isolates with the longest branch came from Sersale and belonged to patients who had glass syringes as risk factor. HCV 2c isolates from the Calabria region shared a common ancestor whose origin was traced back to 1889. Our results suggest that, after its introduction - possibly as a result of population movements between Italy and African Countries during Italian colonialism - HCV 2c spread through multiple risk factors, not including intravenous drug use. So, transmission chains followed a pathway different from other European Countries. Although HCV incidence is decreasing, these ways are still ongoing, possibly justifying stability in the relative prevalence of HCV 2c.