Synonymous co-variation across the E1/E2 gene junction of hepatitis C virus defines virion fitness

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.

Suicide among young people and adults in Ireland: method characteristics, toxicological analysis and substance abuse histories compared

Objective: Information on factors associated with suicide among young individuals in Ireland is limited. The aim of this study was to identify socio-demographic characteristics and circumstances of death associated with age among individuals who died by suicide. Methods: The study examined 121 consecutive suicides (2007–2012) occurring in the southern eastern part of Ireland (Cork city and county). Data were obtained from coroners, family informants, and health care professionals. A comparison was made between 15-24-year-old and 25-34-year-old individuals. Socio-demographic characteristics of the deceased, methods of suicide, history of alcohol and drug abuse, and findings from toxicological analysis of blood and urine samples taken at post mortem were included. Pearson’s χ2 tests and binary logistic regression analysis were performed. Results: Alcohol and/or drugs were detected through toxicological analysis for the majority of the total sample (79.5%), which did not differentiate between 15-24-year-old and 25-34-year-old individuals (74.1% and 86.2% respectively). Compared to 25-34-year-old individuals, 15-24-year-old individuals were more likely to engage in suicide by hanging (88.5%). Younger individuals were less likely to die by intentional drug overdose and carbon monoxide poisoning compared to older individuals. Younger individuals who died between Saturday and Monday were more likely to have had alcohol before dying. Substance abuse histories were similar in the two age groups. Conclusion: Based on this research it is recommended that strategies to reduce substance abuse be applied among 25-34-year-old individuals at risk of suicide. The wide use of hanging in young people should be taken into consideration for future means restriction strategies.