EXPERIMENTAL POLYMICROBIAL PERITONITIS-ASSOCIATED TRANSCRIPTIONAL REGULATION OF MURINE ENDOGENOUS RETROVIRUSES

Despite advancements in understanding the pathophysiology of sepsis, clinical outcomes are variable, and the mortality rate remains high among patients. We investigated whether expression of murine endogenous retroviruses (MuERVs), constituting similar to 10% of the mouse genome, is differentially regulated in response to sepsis-elicited stress signals. ICR mice were subjected to cecal ligation and puncture, and MuERV expression was examined. There was evident regulation (induced or repressed) of MuERV expression in the liver and lung after cecal ligation and puncture. In particular, expression of several variant transcripts was increased, primarily in the liver, at 12 and/or 48 h: nine splicing variants and one 5.06-kb nonspliced transcript. Four novel splicing signals were also identified. Six variant transcripts were presumed to be splicing products of the 5.06-kb transcript, whereas the other three were envelope variants transcribed from at least five MuERV loci. These findings demonstrate that expression of certain MuERVs, including their envelope subgenomic transcripts, are altered during the course of sepsis pathogenesis.