CELLS EXPRESSING THE HUMAN FOAMY VIRUS (HFV) ACCESSORY BET PROTEIN ARE RESISTANT TO PRODUCTIVE HFV SUPERINFECTION

Bet is a foamy virus (FV) accessory protein not required for virus rep lication. The function of Bet is not understood. We report on the gene ration of cell lines stably expressing the HFV Bet protein. In Bet(+) cells, HFV replication was reduced by similar to 3-4 orders of magnitu de compared with control cells. The HFV Bet-expressing cells only part ially resisted infection by the distantly related feline FV (FFV). Pse udotyping experiments, using murine retroviral vectors with an HFV env elope, revealed that the resistance was not due to downregulation of t he unknown HFV receptor. In transfection experiments, using proviral r eporter gene constructs and infectious proviruses, no significant diff erences were detected between Bet(+) and control cells. In infection e xperiments, HFV vectors expressing an indicator gene under control of the HFV promoters showed no activity in Bet(+) cells. The results are best compatible with the hypothesis that the main block to productive superinfection of Bet+ cells occurs at an early stage of replication b etween virus entry and provirus establishment. We suggest that inhibit ion of provirus integration by Bet protein may serve a distinct functi on in the unique foamy virus replication cycle. (C) 1998 Academic Pres s.