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Most notable of these was the initial discovery of a natural recombinant form of HCV circulating in injecting drug users resident in St. This recombinant, labeled 2k/1b, has a 5′ genome region that is most closely related to subtype 2k and a 3′ genome region that is most closely related to the global epidemic subtype 1b, with a single recombination breakpoint located at genomic position 3175 or 3176 in the NS2 gene (20).

Since the discovery of 2k/1b, several other studies have reported both inter- and intragenotypic HCV recombinants in natural populations, although the evidence presented for recombination varies in strength; the weakest studies report only discordant genotyping results between genome regions (which could also result from coinfection), whereas the most convincing studies repeatedly sequence the same recombination breakpoint from independent extractions (thereby excluding the possibility of 8, 19, 28, 29, 42).

The methods introduced here should serve as a model for future phylogenetic investigations of genetic-exchange events in RNA virus populations.

In the course of a study of HCV-infected patients resident in Amsterdam (unpublished data), it was found that HCV genotyping results from the 5′ untranslated and NS5B regions were discordant for 6 (out of 200) patients.

HCV diversity is classified into six main genotypes (genotypes 1 to 6), each of which is further divided into numerous subtypes, and the virus exhibits nucleotide sequence divergences of 30 and 20% at the genotype and subtype levels, respectively (58).