HIV-1 translation and its regulation by cellular factors PKR and PACT

The synthesis of proteins from viral mRNA is the first step towards viral assembly. Viruses are dependent upon the cellular translation machinery to synthesize their own proteins. The synthesis of proteins from the human immunodeficiency virus (HIV) type 1 and 2 RNAs utilize several alternative mechanisms. The regulation of viral protein production requires a constant interplay between viral requirements and the cell response to viral infection. Among the antiviral cell responses, the interferon-induced RNA activated protein kinase, PKR, regulates the cellular and viral translation. During HIV-1 infection, PKR activation is highly regulated by viral and cellular factors. The cellular TAR RNA Binding Protein, TRBP, the Adenosine Deaminase acting on RNA, ADAR1, and the PKR Activator, PACT, play important roles. Recent data show that PACT changes its function from activator to inhibitor in HIV-1 infected cells. Therefore, HIV-1 has evolved to replicate in cells in which TRBP, ADAR1 and PACT prevent PKR activation to allow efficient viral protein synthesis. This proper translation will initiate the assembly of viral particles. (C) 2014 Elsevier B.V. All rights reserved.