Genome-wide changes in expression profile of murine endogenous retroviruses (MuERVs) in distant organs after burn injury.
BACKGROUND
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. 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.


RESULTS
Female 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.


CONCLUSIONS
In 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.
Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California and Department of Surgery, University of California, Davis, Sacramento, CA 95817, USA. yknlee@ucdavis.edu
Young-Kwan
YK
Lee
Alex
A
Chew
Lauren
L
Fitzsimon
Rita
R
Thomas
David
D
Greenhalgh
Kiho
K
Cho
D000818:Animals; D002056:Burns / Q000235:genetics / Q000821:virology*; D020077:Endogenous Retroviruses / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D020869:Gene Expression Profiling; D016678:Genome; D007668:Kidney / Q000821:virology; D008099:Liver / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D014158:Transcription, Genetic