Spouse-to-Spouse Transmission and Evolution of Hypervariable Region 1 and 5’ Untranslated Region of Hepatitis C Virus Analyzed by Next-Generation SequencingReportar como inadecuado




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Hepatitis C virus HCV transmission between spouses remains poorly characterized, largely due to the limited availability of samples from the early stage of infection, as well as methodological constraints. A fifty-eight year-old male developed acute hepatitis C infection and his 53-year old spouse has been HCV-positive for over 10 years. Serum samples were collected from both at the time of acute hepatitis C diagnosis in male baseline and then at 9 and 13 months. Hypervariable region 1 HVR1 and 5’ untranslated region 5’UTR sequences were amplified and subjected to next generation sequencing NGS using a pyrosequencing platform. Genetic variants were inferred by Shorah reconstruction method and compared by phylogenetic and sequence diversity analysis. As the sequencing error of the procedure was previously determined to be ≤ 1.5%, the analysis was conducted with and without the 1.5% cut-off with regard to the frequency of variants. No identical HVR1 variants were identified in spouses at baseline and follow-up samples regardless whether the cut-off was applied or not. However, there was high similarity 98.3% between a minor baseline donor variant 1.7% frequency and the most abundant baseline recipient variant 62.5% frequency. Furthermore, donor and recipient strains clustered together when compared to 10 control subjects from the same area and infected with the same HCV subtype. There was an increase in HVR1 complexity number of genetic variants over time in both spouses. In contrast, the 5-UTR region was stable and of low complexity throughout the study. In conclusion, intrafamilial HCV transmission may be established by a very minor variant and investigation of this phenomenon requires high-sensitivity assays, such as NGS.



Autor: Kamila Caraballo Cortes , Osvaldo Zagordi, Joanna Jabłońska, Agnieszka Pawełczyk, Natalia Kubisa, Karol Perlejewski, Iwona Buk

Fuente: http://plos.srce.hr/



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