A DEFECTIVE HUMAN FOAMY PROVIRUS GENERATED BY PREGENOME SPLICING

Foamy viruses are a group of retroviruses of complex structure which w ere thought to be non-pathogenic. The recent demonstration of neurolog ical diseases in mice transgenic for human foamy virus (HFV) and the h igh prevalence of HFV sequences in Graves' disease question this idea. By PCR, we have detected HFV sequences with a non-random deletion in the bel1 transactivator gene in other autoimmune conditions. Sequence analysis revealed that this deleted area corresponds to the excision o f a known intron in bet, one of HFV's regulatory genes. The same pheno menon was observed in both acute and chronic infections, in vitro or i n vivo, although the deleted forms were distinctly more abundant in ch ronic states. The viral DNA containing the bel1 deletion is apparently part of an otherwise complete genome, strongly suggesting that this p rovirus derives from the reverse transcription of a spliced pregenomic RNA. Bel1-spliced provirus was shown to be defective when transfected into permissive cells. However, co-expression with the Bel1 transacti vator led to functional trans-complementation and formation of viral p articles. Splicing of the genome may be an important factor in HFV bio logy: genomes with the deletion may either interfere with wild-type vi rus expression or alter host cell functions through background express ion of viral regulatory