SPECIFIC-INHIBITION OF VIRAL PROTEIN-SYNTHESIS IN HIV-INFECTED CELLS IN RESPONSE TO INTERFERON TREATMENT

The mechanism of action of different types of interferons (IFN-alpha, -beta, and -gamma) against human immunodeficiency virus (HIV)-1 infect ion was investigated in chronically infected monocytoid U937 cells and during an acute infection of the T lymphoblastoid CEM cells. Two chro nically infected U937 cell populations, obtained independently (referr ed to as type A and B cells), were analyzed for their response to IFNs . In type A cells, IFNs mainly inhibited virus particle release, where as in type B cells, the anti-HIV effect of IFNs cells was found to be largely due to a specific inhibition of viral protein synthesis withou t any apparent effect on total cellular protein synthesis. Interesting ly, such a differential inhibition of HIV protein synthesis could also be demonstrated in acutely infected CEM cells in response to treatmen t with IFN-a. Both in chronically infected U937 type B and acutely inf ected CEM cells, equivalent amounts of nuclear and cytoplasmic HIV-1 m RNA were detected in control and IFN-treated cells in spite of at leas t 80% inhibition of HIV protein synthesis. Analysis of the distributio n of cellular and viral mRNAs on polysomes in HIV-1-infected cells dem onstrated that IFN treatment induces a specific block on viral mRNA tr anslation. These results indicate that the antiviral mechanism of IFN on later stages of HIV replication cycle may be partly due to the inhi bition of HIV mRNA translation, besides an effect on virus budding or release.