TYRPHOSTIN AG-555 INHIBITS EARLY AND LATE STAGES OF MOLONEY MURINE LEUKEMIA-VIRUS REPLICATION CYCLE

We have previously shown that certain tyrphostin derivatives, known as protein tyrosine blockers, inhibited Moloney murine leukemia virus (M o-MuLV) replication in acutely and chronically infected NIH/3T3 cells, without affecting cell viability or growth. In our present work, we e xamined the stages in the viral life cycle that are affected by tyrpho stin AG-555. We found that this drug inhibited the integration of the viral DNA into the host genome in acutely infected cells. This compoun d also reduced the level of viral RNA and specifically inhibited viral protein synthesis in NIH/3T3/Mo-MuLV chronically infected cells while no effect on the cellular beta-actin was observed. Since tyrphostin A G-555 inhibited both the early stages (integration process) and the la te stages (viral protein synthesis) in the virus life cycle, it offers a potential advantage over other compounds which affect only one stag e in the viral life cycle. Therefore, tyrphostin AG-555 may be conside red as a potent antiretroviral drug.