SPLICED HUMAN ENDOGENOUS RETROVIRAL HERV-H ENV TRANSCRIPTS IN T-CELL LEUKEMIA-CELL LINES AND NORMAL LEUKOCYTES - ALTERNATIVE SPLICING PATTERN OF HERV-H TRANSCRIPTS

The majority of human endogenous retroviral HERV-H elements in the hum an genome have large deletions in pol and lack most of env, 5-10% are more or less complete with a potentially immunosuppressive transmembra ne protein-encoding env region, Spliced HERV-H env transcripts were de tected in T-cell leukaemia cell lines and lymphocytes from healthy blo od donors by using RT-PCR. The transcripts all contained a splice dono r in the leader region downstream from the primer-binding site and a p reviously unreported splice acceptor in the integrase-encoding region of pol, absent in the HERV-H deletion elements. In singly spliced tran scripts the leader and integrase regions were joined directly whereas in multiply spliced transcripts they were joined with an alternative e xon from the protease-encoding region located between the two regions. env transcripts from three different HERV-H elements were identified: one element similar to a HERV-H consensus sequence was primarily ampl ified from the T-cell leukaemia cell lines and two other more defectiv e elements were amplified from normal lymphocytes. One of these elemen ts was shown to be a reintegrated spliced transcript where the proteas e and integrase regions were joined, removing most of pol but leaving gag intact. Other spliced transcripts, joining the protease region and the 3'-LTR, were also amplified. The fact that HERV-H elements with a n intact env splice acceptor also use the splice sites in the protease -encoding region suggests that this unusual multiple splice pattern co uld have a biological function in the intact HERV-H.