CHARACTERIZATION OF NOVEL REVERSE-TRANSCRIPTASE ENCODING HUMAN ENDOGENOUS RETROVIRAL SEQUENCES SIMILAR TO TYPE-A AND TYPE-B RETROVIRUSES - DIFFERENTIAL TRANSCRIPTION IN NORMAL HUMAN TISSUES

The polymerase chain reaction was used to amplify genomic DNA and reve rse-transcribed RNA from human lymphocytes, using primers derived from conserved regions within the retroviral reverse transcriptase. Sequen cing of 33 cloned amplification products revealed that a variety of se quences with similarity to mouse mammary tumor virus, mouse intraciste rnal A particle, and human endogenous retrovirus K10 were detected wit h this primer pair. The sequences were divided into six subgroups, wit h a nucleotide sequence dissimilarity of about 25% between the subgrou ps. Members within five of the subgroups were most closely related to human endogenous retrovirus K10 and mouse mammary tumor virus, whereas sequences of the sixth subgroup also showed similarity to mouse intra cisternal A particle. Ten of the sequences had open reading frames wit h preference for silent mutations at conserved sites. Southern blot an alysis showed that some HML (human endogenous MMTV-like) subgroups (HM L-4 and HML-5) were present in a few copies (about 5), whereas others (HML-1 to HML-3 and HML-6) were present in at least 10 to 20 copies pe r genome. Northern (RNA) blot analysis revealed that several of the su bgroups are differentially expressed in human normal tissues. A comple x pattern of transcripts from about 12 to 1.4 kb was found in several of the tissues tested. However, the most abundant expression was detec ted in lung (all subgroups), skeletal muscle (HML-4 and HML-5), placen ta (HML-2 and HML-5), and kidney (HML-2, HML-3 and HML-5). Expression of reverse transcriptase sequences in human tissues may have biologica l consequences. The described sequences are similar to elements which cause carcinoma and are immunoregulatory in mice. It remains to be see n whether human sequences also have such functions.