Synonymous co-variation across the E1/E2 gene junction of hepatitis C virus defines virion fitness
| dc.contributor.author | Palmer, Brendan A. | |
| dc.contributor.author | Fanning, Liam J. | |
| dc.date.accessioned | 2016-12-08T13:00:40Z | |
| dc.date.available | 2016-12-08T13:00:40Z | |
| dc.date.issued | 2016-11-23 | |
| dc.date.updated | 2016-12-08T12:51:01Z | |
| dc.description.abstract | Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3′-end of E1 highly conserved and the 5′-end of E2 highly heterogeneous. This gene junction is also believed to contain structured RNA elements, with a growing body of evidence suggesting that such structures can act as an additional level of viral replication and transcriptional control. We have previously used ultradeep pyrosequencing to analyze an amplicon library spanning the E1/E2 gene junction from a treatment naïve patient where samples were collected over 10 years of chronic HCV infection. During this timeframe maintenance of an in-frame insertion, recombination and humoral immune targeting of discrete virus sub-populations was reported. In the current study, we present evidence of epistatic evolution across the E1/E2 gene junction and observe the development of co-varying networks of codons set against a background of a complex virome with periodic shifts in population dominance. Overtime, the number of codons actively mutating decreases for all virus groupings. We identify strong synonymous co-variation between codon sites in a group of sequences harbouring a 3 bp in-frame insertion and propose that synonymous mutation acts to stabilize the RNA structural backbone. | en |
| dc.description.status | Peer reviewed | en |
| dc.description.version | Published Version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.articleid | e0167089 | |
| dc.identifier.citation | Palmer, B. A. and Fanning, L. J. (2016) ‘Synonymous co-variation across the E1/E2 gene junction of Hepatitis C virus defines virion fitness’, PLoS ONE 11(11), e0167089 (18pp). doi:10.1371/journal. pone.0167089 | en |
| dc.identifier.doi | 10.1371%2Fjournal.pone.0167089 | |
| dc.identifier.endpage | 18 | en |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.issued | 11 | en |
| dc.identifier.journaltitle | PLoS ONE | en |
| dc.identifier.startpage | 1 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/3361 | |
| dc.identifier.volume | 11 | en |
| dc.language.iso | en | en |
| dc.publisher | Public Library of Science | en |
| dc.rights | © 2016, Brendan A. Palmer and Liam J. Fanning. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | E1/E2 gene junction | en |
| dc.subject | Synonymous co-variation | en |
| dc.subject | RNA | en |
| dc.subject | Mutation | en |
| dc.title | Synonymous co-variation across the E1/E2 gene junction of hepatitis C virus defines virion fitness | en |
| dc.type | Article (peer-reviewed) | en |
