HIV Rev – beyond nuclear export
The year 2008 marked the 25th year of human immunodeficiency virus (HIV) research. Such a milestone often prompts an assessment of what has been accomplished and where gaps remain in our knowledge. As with most things in their mid-twenties, HIV research has achieved a great deal, but there is still a lot to learn. This dichotomy is exemplified by the viral regulatory protein Rev. Most reviews specifically addressing Rev function date from the 1990s; this is surprising, given the diversity of roles attributed to it since then.
Rev is best known to stimulate nucleocytoplasmic transport of incompletely spliced viral RNAs. Rev binds to RNAs containing the Rev-response element (RRE), which is contained within all incompletely spliced RNAs. The amino-terminal domain of Rev contains the RNA-binding activity of the protein and is an arginine-rich sequence that also serves as the nuclear-localization signal. Regions surrounding the amino-terminal domain are proposed to be important in the multimerization of the protein onto the RNA. The carboxy-terminal domain, originally referred to as the activation domain, contains the nuclear-export signal. The combined effects of the nuclear-localization and nuclear-export signals allow Rev to shuttle in and out of the host cell nucleus. This allows incompletely spliced RNAs access to the translation machinery and makes full-length genomic RNA available for encapsidation into virus particles.
The HIV Rev protein remains a hot topic. This review revisits the insights that have been gained into the control of gene expression by Rev and speculates on where current research is leading. It outlines what is known about the role of Rev in translation and encapsidation and how these are linked to its more traditional role of nuclear export, underlining the multifaceted nature of this small viral protein. It also discusses what more is to be learned in these fields and why continuing research on these 116 amino acids and understanding their function is still important in devising methods to combat AIDS.
Rev: beyond nuclear export. 2009 J Gen Virol. 90: 1303-1318
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- Tat – the versatile protein of HIV-1
- Why is HIV a pathogen?
- How does HIV cause AIDS?
- Re-awakening old genes to help in the fight against viruses
- HIV is evolving rapidly to escape the immune system
Tags: Biology, disease, Health, HIV/AIDS, Medicine, Microbiology, Science, Virology, virus
