Human monocytes possess a serine protease activity capable of degrading HIV-1 reverse transcriptase in vitro

Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) play s a central role in the virus replication cycle. We found that HIV-1 RT was rapidly degraded when incubated with cell extracts obtained from human per ipheral blood cells. The proteolytic activity responsible for the in vitro degradation of RT was present in monocytes and their precursors. Interestin gly, this activity was downregulated upon cell activation or differentiatio n along the macrophage pathway. The proteolytic process appears specific fo r HIV-1 RT since other HIV-1 proteins were not degraded upon incubation in the same extracts. Although the degradation of RT was unaffected by specifi c proteasome inhibitors, it could be inhibited by PMSF and aprotinin, sugge sting the involvement of a serine protease. Upon cell fractionation, this s erine protease was found to be associated with the microsomal fraction and displayed an apparent molecular weight of approximately 2000 kDa, as determ ined by gel filtration. Our results suggest that a giant serine protease, d ifferent from tripeptidyl peptidase II, is involved in the in vitro degrada tion of HIV-1 RT. The possibility of an in vivo interaction between HIV-1 R T and a cell-type-specific serine protease is discussed. (C) 2001 Academic Press.