INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND VACCINIA VIRUS-INFECTION BY A DOMINANT-NEGATIVE FACTOR OF THE INTERFERON REGULATORY FACTOR FAMILY EXPRESSED IN MONOCYTIC CELLS

ICSBP is a member of the interferon (IFN) regulatory factor (IRF) fami ly that regulates expression of type I interferon (IFN) and IFN-regula ted genes, To study the role of the IRF family in viral infection, a c DNA for the DNA-binding domain (DBD) of ICSBP was stably transfected i nto U937 human monocytic cells,Clones that expressed DBD exhibited a d ominant negative phenotype and did not elicit antiviral activity again st vesicular stomatitis virus (VSV) infection upon IFN treatment. Most notably, cells expressing DBD were refractory to infection by vaccini a virus (VV) and human immunodeficiency virus type 1 (HIV-1). The inhi bition of VV infection was attributed to defective virion assembly, an d that of HIV-1 to low CD4 expression and inhibition of viral transcri ption in DBD clones. HIV-1 and VV were found to have sequences in thei r regulatory regions similar to the IFN-stimulated response element (I SRE) to which IRF family proteins bind. Accordingly, these viral seque nces and a cellular ISRE bound a shared factor(s) expressed in U937 ce lls. These observations suggest a novel host-virus relationship in whi ch the productive infection of some viruses is regulated by the IRF-de pendent transcription pathway through the ISRE.