INHIBITION OF THE DSRNA-DEPENDENT PROTEIN-KINASE BY A PEPTIDE DERIVEDFROM THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT PROTEIN

The human immunodeficiency virus (HIV) is the etiologic agent leading to the development of acquired immunodeficiency syndrome (AIDS). Inter ferons (IFNs) are known for eliciting antiviral responses from cells, and studies have indicated that infection with HIV induces the product ion of IFN. Previous studies have shown that the trans-acting response element (TAR) sequence of HIV-1 mRNA can activate the IFN-induced dou ble-stranded (ds) RNA-dependent protein kinase (DAI). DAI, when activa ted, is a potent inhibitor of protein synthesis and has been implicate d in mediating part of IFN's antiviral activity. Here, we report that a synthetic peptide containing the basic region of HIV Tat protein is effective in preventing the activation of DAI. Evidence is presented t hat indicates that the Tat peptide exerts its effect by binding to the TAR RNA sequence and thus preventing this RNA from binding to and act ivating DAI. It appears that in addition to its role in trans-activati on, the tat protein may also function to overcome the antiviral activi ty of IFN by regulating DAI activity. Thus, inhibition of DAI by the T at protein early in the life cycle of HIV may provide a mechanism by w hich the virus can escape a translational block imposed by the kinase.