Injury-associated induction of two novel and replication-defective murine retroviral RNAs in the liver of mice

Injury can alter the expression of numerous genes in affected tissues as well as in distant organs. The mouse genome harbors numerous copies of endogenous murine leukemia virus (MuLV)-related retroviral sequences. Mouse liver tissues harvested after burn injury were subjected to RT-PCR analysis to investigate the regulation of MuLV-related sequences using a primer set capable of amplifying the full-length transcript. A doublet of approximately 5-kb was transiently up-regulated at 3 and 6 h after injury. Sequence analyses revealed that these are novel defective endogenous retroviral sequences (MuLV(LI-8) and MuLV(LI-12)), which are predominantly characterized by major deletions in pol and env genes. The MuLV(LI-8) clone is 4.85 kb long and the deduced gag polypeptide sequence was almost identical to a previously reported replication-defective retroviral sequence associated with immunesuppression. In the MuLV(LI-12) clone of 5.06 kb, there were two truncated gag open reading frames (ORFs) and 1 pol ORF fused to the C-terminus of the env p15E. Furthermore, the ORFs for the unique gag p12 presumed to be responsible for the immunesuppression were present in both clones. These novel replication-defective MuLVs may participate in the pathogenesis of distant organs after injury.