)[1]. Overall sequence divergence ranges from 31% to 33% among genotypes and from 20% to 25% among subtypes[1,2]; in a single patient, cloned E1/E2 sequences may differ by up to 10%. The reason for this great variation is a high mutation rate and high level of viral replication through an error prone RNA polymerase without proofreading capacity. Consequently, selleck chemicals llc in the infected individual, the virus circulates as a complex viral quasispecies[3] whose composition is subject to continuous changes due to competitive selection[4] and interactions among variants of with different levels of fitness[5]. The calculated average rate of fixation of mutations has consistently been found to range between 1.1 and 1.5 �� 103 mutations per site and per year[6,7].

The rate of fixation of mutations is not evenly distributed throughout the genome, which has highly variable regions within the envelope coding genes and well conserved regions, such as the 5�� untranslated region (5��UTR). The practical consequence of the high conservation at 5��UTR for HCV genotyping is that this region contains insufficient variation to solve HCV classification at the level of viral subtypes[8]. Furthermore, genotype 6 variants other than 6a and 6b show 5��UTR sequences identical or similar to those of type 1 and, therefore, cannot be differentiated[9-11]. It has been reported that sequence analysis of the highly conserved region in NS5B known as the ��Okamoto region�� (nt 8282 to 8610 in the H77 reference genome)[8] provides the best concordance with the full length genome phylogeny for precise genotype identification.

The same primers can amplify genotypes 1 to 5, and they are less efficient for genotype 6 isolates, but they facilitate analysis and classification of the amplified sequences[11]. The prevalence of HCV infection in Argentina has been reported at 1.5% when all age groups are considered, and up to 2.0%-2.5% in adults[12], a rate in keeping with the value reported by the Argentinian Consensus on Hepatitis C (approximately 2%) in 2007. A higher prevalence (4.9%-5.7%) has been described in small rural communities[13,14]. HCV genotype distribution in Argentina in groups at risk of HCV infection (e.g., transfusion patients, hemodialysis patients, intravenous drug users, healthcare workers) has been reported at 53.5% for genotype 1, 23% for genotype 2 (mainly by subtype 2c [HCV-2c]), 8.

6% for genotype 3, and 14.8% for mixed infections[15]. Similar results have been reported in studies on sequences deposited in GenBank (GB) and analyses by the Los Alamos database http://hcv.lanl.gov, Carfilzomib with few genotype distribution changes (79.5% for genotype 1, 13.9% for genotype 2, 3.9% for genotype 3, 2.4% for genotype 4), but with some differences depending on the HCV subgroup at risk studied[16-18]. Phylogenetic characterization of genotype 4 isolates from Argentina has traced an independent origin of the three sequences studied[17].