Transmissibility of intra-host hepatitis C virus variants
| Autor: | David S. Campo, June Zhang, Sumathi Ramachandran, Yury Khudyakov |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | BMC Genomics, Vol 18, Iss S10, Pp 11-19 (2017) |
| Druh dokumentu: | article |
| ISSN: | 1471-2164 02947838 |
| DOI: | 10.1186/s12864-017-4267-4 |
| Popis: | Abstract Background Intra-host hepatitis C virus (HCV) populations are genetically heterogeneous and organized in subpopulations. With the exception of blood transfusions, transmission of HCV occurs via a small number of genetic variants, the effect of which is frequently described as a bottleneck. Stochasticity of transmission associated with the bottleneck is usually used to explain genetic differences among HCV populations identified in the source and recipient cases, which may be further exacerbated by intra-host HCV evolution and differential biological capacity of HCV variants to successfully establish a population in a new host. Results Transmissibility was formulated as a property that can be measured from experimental Ultra-Deep Sequencing (UDS) data. The UDS data were obtained from one large hepatitis C outbreak involving an epidemiologically defined source and 18 recipient cases. k-Step networks of HCV variants were constructed and used to identify a potential association between transmissibility and network centrality of individual HCV variants from the source. An additional dataset obtained from nine other HCV outbreaks with known directionality of transmission was used for validation. Transmissibility was not found to be dependent on high frequency of variants in the source, supporting the earlier observations of transmission of minority variants. Among all tested measures of centrality, the highest correlation of transmissibility was found with Hamming centrality (r = 0.720; p = 1.57 E-71). Correlation between genetic distances and differences in transmissibility among HCV variants from the source was found to be 0.3276 (Mantel Test, p = 9.99 E-5), indicating association between genetic proximity and transmissibility. A strong correlation ranging from 0.565–0.947 was observed between Hamming centrality and transmissibility in 7 of the 9 additional transmission clusters (p |
| Databáze: | Directory of Open Access Journals |
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