( mplex a group of four proteins known ...)Shutting down the HIV assembly line

Through a series of experiments, the group demonstrated that the AP-3 delta subunit interacts with Gag to direct it to the multivesicular body. Disruption of the interaction, using a specific piece of the AP-3 subunit, eliminated Gag trafficking to the multivesicular body and diminished HIV particle formation in cells.

"The significance of this paper comes from really identifying how Gag gets to the multivesicular body and in demonstrating that if you block that trafficking step specifically, you block production of particles," Spearman said. "That says this is not a dead-end pathway, but that it is part of the normal, productive assembly pathway."

The newly identified early step in the HIV assembly process could be a target for a new generation of drugs to combat the virus. No existing anti-HIV drugs disrupt particle assembly or the movement of Gag in the cell.

"We have hopes of identifying compounds that inhibit this Gag-AP-3 interaction and that may lead to new efforts to treat HIV infection," Spearman said.

Such drugs should be very specific, he said, since it should be possible to block Gag's interaction with AP-3 without disrupting AP-3 function in the cell. And by targeting an early step in HIV particle assembly, an inhibitor of this sort would be expected to block viral replication in cells that complete assembly at the multivesicular body as well as those that assemble particles at the cell membrane.