12th International AIDS Conference Geneva, Switzerland - June 28-July 3, 1998

Int Conf AIDS 1998 Jun 28-Jul 3; 12:23-4 (abstract no. 11208)

Loewer J, Magin C, Loewer R
Paul-Ehrlich-Institut, Langen, Germany.

OBJECTIVES: HERV-K is a moderately repetitive endogenous Retrovirus family in the genomes of primates and humans. It codes for the Retrovirus-like particles HTDV detected in human teratocarcinoma cell lines. HTDV/HERV-K is related to D-type Retroviruses. However HERV-K expresses a protein-cORF-that has no counterpart in D-type Retroviruses. In complexly regulated Retroviruses (e.g. lentiviruses and T-cell leukemia viruses), the coordinated expression of accessory and structural genes depends on the presence of a trans-acting viral protein (Rev or Rex) and of a responsive element (RRE or RxRE) on the viral RNA transcripts. cORF has some properties, similar to Rev and Rex namely a leucine rich domain and a nuclear localization. Assuming that cORF is a Rev homolog, we set out to identify a cORF responsive element.

METHODS: The model system we used has been established and kindly provided by B. Felber and G. Pavlakis (Frederick). In short, a construct composed by a HIV 5' LTR, a portion of the HIV gag gene and the HIV RRE is expressed in a cell line constitutively producing Tat. HIV p24 can only be detected when a functional Rev is provided from a co-transfected plasmid. By inserting HERV-K gag sequences instead of HIV gag, we confirmed that HERV-K gag expression is under the control of a Rev/RRE like function. In this study, we have exchanged the HIV RRE sequences by HERV-K sequences and tested for their ability to replace the HIV Rev/RRE function in co-transfection experiments with Rev and cORF expressing plasmids.

RESULTS: We have identified an element with RRE function spanning parts of the 3' U3 and the R region that is able to regulate Gag and Env expression from subgenomic and full length expression vectors in a cORF dependent manner. The element is designed RcRE.

CONCLUSION: We found that the protein expression of HERV-K is regulated in a manner that has been described only for lentiviruses and human T-cell leukemia viruses up to now. The localization is identical with that of the RxRE of HTLV I. Therefore this regulation system seems to have evolved in virus that are thirty million years older than HIV and HTLV.

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