Abstract
BackgroundPrevious studies have shown that burn-elicited stress signals alter expression of certain murine endogenous retroviruses (MuERVs) in distant organs of mice. These findings suggest that MuERVs may participate in a network of pathophysiologic events during post-burn systemic response. To gain a better understanding of the biological roles of MuERVs in post-burn systemic response, we examined the genome-wide changes in the MuERV expression profiles in distant organs and the biological properties of the putative-burn related MuERVs were characterized.ResultsFemale C57BL/6J mice were subjected to an approximately 18 % total body surface area flame burn and tissues (liver, lung, and kidney) were harvested at 3 hours and 24 hours after injury. The changes in the MuERV expression profiles in these tissues were examined by RT-PCR using a primer set flanking the non-ecotropic MuERV U3 promoter region within the 3' long terminal repeat. There were differential changes in the expression profiles of MuERV U3 regions after injury in all three tissues examined. Subsequently, a total of 31 unique U3 promoter sequences were identified from the tissues of both burn and no burn mice. An analysis of viral tropisms revealed that putative MuERVs harboring these U3 promoter sequences were presumed to be either xenotropic or polytropic. Some putative transcription regulatory elements were present predominantly in U3 promoter sequences isolated from burn and no burn mice, respectively. In addition, in silico mapping using these U3 sequences as a probe against the mouse genome database identified 59 putative MuERVs. The biological properties (coding potentials for retroviral polypeptides, primer binding sites, tropisms, branching ages, recombination events, and neighboring host genes) of each putative MuERV were characterized. In particular, 16 putative MuERVs identified in this study retained intact coding potentials for all three retroviral polypeptides (gag, pol, and env). None of the putative MuERVs identified in this study were mapped to the coding sequences of host genes.ConclusionIn this study, we identified and characterized putative MuERVs whose expression might be altered in response to burn-elicited systemic stress signals. Further investigation is needed to understand the role of these MuERVs in post-burn systemic pathogenesis, in particular, via characterization of their interaction with host genes, MuERV gene products, and viral activities.
Highlights
Previous studies have shown that burn-elicited stress signals alter expression of certain murine endogenous retroviruses (MuERVs) in distant organs of mice
Differential alterations in MuERV expression profiles in distant organs of mice after burn To investigate the changes in genome-wide MuERV expression after burn, we examined the transcription profiles of non-ecotropic MuERV U3 regions in the liver, lungs, and kidney from both burn and no burn mice by reverse transcriptase (RT)-PCR (Figure 1)
The U3 regions were selected for expression analysis because of their highly polymorphic sequences among the MuERV population compared to the rest of the viral genome
Summary
Previous studies have shown that burn-elicited stress signals alter expression of certain murine endogenous retroviruses (MuERVs) in distant organs of mice. These findings suggest that MuERVs may participate in a network of pathophysiologic events during post-burn systemic response. Certain ERVs retain the full coding potentials for all or individual retroviral polypeptides [2,3] It has been well-documented that retroviral long terminal repeats (LTRs), which harbor unique U3 promoter and enhancer sequences, are capable of directly regulating the transcriptional activities (e.g., primary transcription, splicing, and polyadenylation) of neighboring host genes [4,5,6]. In conjunction with the diversity of the ERV U3 promoter sequences, these findings infer active participation of ERVs in a range of normal physiologic as well as pathologic events of the host [7,8]
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