A MACROPHAGE-LIKE CELL MODEL FOR TESTING ANTI-CMV DRUGS

Monocyte/macrophage cells can be infected with human cytomegalovirus ( HCMV) and could be a reservoir and a vehicle for virus spread in infec ted patients, The monocytic-like cell line THP-1 differentiated along the monocyte pathway with a phorbol ester (phorbol 12-myristate 13-ace tate, PMA) for 24h was infected with cell free-supernatant of Towne CM V-strain infected fibroblasts MRC-5. We designed experiments to study the replication of HCMV in PMA treated THP-1 cells, exposed to DHPG (C ymevan(R), ganciclovir, Syntex). We incubated PMA treated THP-1 cells with DHPG for one to five days at 37 degrees C before or after the inf ection, The cells were cultivated for 5 days at 37 degrees C then supe rnatants of culture were collected and they were added to fibroblast c ultures. The infection of the fibroblasts was studied on the basis of immune detection of viral immediate early antigens (IEA) in nucleus 24 h after culture, Incubation of infected THP-1 cells with 11.1 mu M DHP G for 5 days at 37 degrees C resulted in 95 +/- 2% inhibition of the r eplication whereas incubation of the infected cells with the same conc entration of DHPG for two days resulted in 50 +/- 5% inhibition, Pretr eatment of cells with DHPG for 5 days induced a 50 +/- 4% decrease of the level of infectious particles produced by HCMV infected cells. Thi s is the first report of the antiviral effect of DHPG in macrophagic-l ike cells.