Differential modulation of host cell and hiv gene expression by combinations of avarol and AZT in vitro

Abstract

Human immunodeficiency virus type 1 (HIV-1) gene expression is modulated by some virus-encoded proteins, possibly acting at multiple levels of control, which are also known to be involved in the regulation of gene expression in uninfected cells (transcriptional, post-transcriptional, nucleocytoplasmic transport, and translational control). Two anti-HIV-1 drugs, Avarol and 3'-azido-3'-deoxythymidine, which inhibit viral replication by differential mechanisms, were used to study the role of cytoplasmic factors in independent regulation of host cell and viral gene expression. Both drugs were found to inhibit viral replication and synthesis of virus-encoded protein in a synergistic manner, while at cytostatic concentrations, both compounds act antagonistically. ATP-induced transport of viral messengers from isolated nuclei is enhanced by total cytosolic protein from HIV-1-infected cells; a strong increase of the nucleocytoplasmic transport of pol mRNA was measured and, to a lesser extent the transport of certain cellular mRNA (e.g. interleukin-2) was augmented, while the transport of other cellular mRNA (actin) was not affected at all.