CD14-dependent modulation of transcriptional activities of endogenous retroviruses in the lung after injury.

Lipopolysaccharide (LPS) plays a central role in the pathogenesis of distant organs after burn. Recent studies demonstrated the regulation of mouse endogenous retroviruses (MuERVs) in several organs after burn. In this study, the role of CD14, a LPS receptor, in burn-mediated regulation of MuERV expression in the lung was investigated. CD14 knockout (KO) and wild type (WT) mice were subjected to burn followed by RT-PCR analysis of alterations in the MuERV expression in the lung 1 day after injury. Even without injury, CD14 KO mice had a unique profile of MuERV expression compared to WT. Three bands (Lung-1, Lung-2, and Lung-3) in CD14 KO were downregulated after injury. Lung-2 and Lung-3 transcripts were almost identical to 2 previously described defective env transcripts of MuERVs, respectively. The Lung-1-1 transcript was a double spliced message generated by the env and a set of novel splicing signals, whereas the Lung-1-2 transcript was a defective env transcript. Only the Lung-1-1 transcript had a significant ORF capable of encoding a gag-pol fusion polypeptide. Putative proviral sequences of Lung-1-1 and Lung-1-2 transcripts were mapped to chromosomes 4 and 11, respectively. The results from this study suggest that the absence of CD14 expression in CD14 KO mice contributes to the transcriptional regulation of MuERVs in the lung after injury.