HIV accessory proteins: Leading roles for the supporting cast

Considering that a set of three genes is sufficient for the replication of most retroviruses, the human and simian immunodeficiency viruses (HIV and SIV) exhibit a surprising degree of genomic complexity. HIV-1 contains no less than six open reading frames in addition to the prototypic gag, pol, and env coding sequences (see Figure 1). Two of these supplementary genes, tat and rev, are absolutely necessary for virus growth: Tat is a major transactivator of the proviral long terminal repeat (LTR), and Rev acts posttranscriptionally to ensure the switch from the early to the late phase of viral gene expression. In contrast, nef, vpu, vif, vpr, and the HIV-2 and SIV vpx genes encode factors that are dispensable for virus growth in many in vitro systems and are thus commonly called accessory proteins. Nevertheless, the high degree of conservation of these products indicate that they fulfill crucial functions in vivo. Exciting new studies are shedding light on these functions and reveal surprising interactions between HIV and its host cell.