Arch Virol (2004) 149: 2215–2233
CD14-mediated alterations in transcription
and splicing of endogenous retroviruses
K. Cho, T. N. Pham, T. Chamberlain, J. Boonyaratanakornkit,
and D. G. Greenhalgh
Burn Research, Shriners Hospitals for Children Northern California
and Department of Surgery, University of California at Davis,
Sacramento, CA, U.S.A.
Received February 3, 2004; accepted April 7, 2004
Published online June 22, 2004
Summary. Increase in systemic levels of lipopolysaccharide (LPS) contributes to
the pathogenesis of distant organ injury after burn. Stress signals elicited from burn
inﬂuence transcriptional activities of mouse endogenous retroviruses (MuERVs)
in various distant organs. The involvement of LPS pathways in the burn-mediated
regulation of MuERVs in the spleen was investigated in this study. Spleen harbors
substantial numbers of tissue macrophages, a key responder to LPS stimulation.
Spleen tissues collected from CD14 (LPS receptor) knockout (KO) and wild type
(WT) mice after burn were subjected to RT-PCR analysis of MuERV expression.
There was a substantial induction of 2 bands and a marked downregulation of
a band in CD14 KO mice compared to WT mice after burn. Sequence analysis
of these CD14- and burn-dependent bands identiﬁed 3 new alternatively spliced
and 2 defective env transcripts of MuERVs as well as novel splicing signals.
Chromosomal loci of putative MuERVs sharing the unique U3 sequences of
these transcripts were mapped by surveying the entire genome of C57BL/6J mice.
In addition, coding potentials, transcriptional regulatory elements, and adjacent
cellular genes of these putative MuERVs were analyzed. The results from these
studies suggest that injury-triggered LPS/CD14 signaling events play roles in
the transcriptional regulation of certain MuERVs carrying unique U3 promoter
Note: The nucleotide sequence data reported in this paper is available from GenBank
database under the accession numbers of AY349138 (SP(B)1-1), AY349139 (SP(NB)1),
AY349140 (SP(B)1-2), AY349141 (SP(B)1-3), and AY349142 (SP(B)2).