The interferon-induced protein kinase R: the base of a riboprotein scaffolding regulating the human immunodeficiency virus

Abstract

The interferon-induced RNA-activated Protein Kinase (PKR) targets the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α) whose phosphorylation blocks translation initiation of cellular and viral mRNAs. PKR is activated at the beginning of human immunodeficiency virus (HIV) infection by low levels of the HIV Transactivation Response (TAR) RNA and by the cellular PKR Activator (PACT), which contributes to a reduced viral replication. During HIV replication, the viral Tat protein and high production of TAR RNA decrease PKR activation. The cellular TAR RNA Binding Protein (TRBP) and Adenosine Deaminase Acting on RNA (ADAR1) also prevent PKR activation, while HIV expression changes PACT function to become a PKR inhibitor. Therefore, HIV recruits viral and cellular factors to counteract PKR antiviral activity. In addition, PKR antiviral function was positively selected during evolution due to contacts with viral factors inhibiting its function. The riboprotein scaffolding such as the one that inhibits PKR during HIV replication may exist for other antiviral factors.

Keywords: HIV; PKR; antiviral; interferon.