Effects of IFN alpha on late stages of HIV-1 replication cycle

IFN alpha causes a modest reduction of HIV-1 expression in chronically infe cted monocytoid U937 cells. However, the ratio between cell-associated and shed viral p24 antigen is altered, being the cell-associated fraction dose- dependently enhanced by IFN. Furthermore, a significant decrease of infecti vity of both cell-associated and shed material is observed. Transmission el ectron microscopy of IFN-treated cells revealed virus assembly being strong ly inhibited, with the production of morphologically altered (tear-drop sha ped) virus particles. Proteolytic processing of gag proteins appeared to be normal in IFN-treated cultures. However, virions shed from IFN-treated cel ls showed a markedly reduced incorporation of virus-specific gp120 and cell -derived ICAM-1 by the virus envelope. Additionally, these particles showed a significantly decreased ability to become bound to CD4+ target cells, ac counting for, at least in part, the observed decrease of infectivity. Taken together the data suggest that, in chronically infected cells, IFN alpha c an affect late stages of HIV-1 replication, by inhibiting virus assembly an d release, and by reducing the infectivity of shed virions. The latter effe ct seems to be due, at least in part, to altered incorporation of surface g lycoproteins and defective particle formation. The relationship between imp aired gp120 incorporation and altered morphogenesis of HIV-1 virions is und er investigation. (C) Societe francaise de biochimie et biologie moleculair e/Elsevier, Paris.