Abstract
The late Nobel Laureate Sir Peter Medawar once memorably described viruses as ‘bad news wrapped in protein’. Virus assembly in HIV is a remarkably well coordinated process in which the virus achieves extracellular budding using primarily intracellular budding machinery and also the unusual phenomenon of export from the cell of an RNA. Recruitment of the ESCRT system by HIV is one of the best documented examples of the comprehensive way in which a virus hijacks a normal cellular process. This review is a summary of our current understanding of the budding process of HIV, from genomic RNA capture through budding and on to viral maturation, but centering on the proteins of the ESCRT pathway and highlighting some recent advances in our understanding of the cellular components involved and the complex interplay between the Gag protein and the genomic RNA.
Highlights
The late Nobel Laureate Sir Peter Medawar once memorably described viruses as ‘bad news wrapped in protein’
Review It is over 20 years since the first striking pictures of a failure in the terminal budding process of Human immunodeficiency virus (HIV) were published [1]. It took over three years for the findings to be confirmed and validated [2], and this marked the beginning of our understanding of the role of the Endosomal sorting complex required for transport (ESCRT) system in the budding of HIV and subsequently in other enveloped viruses
Insights gained from HIV have revealed a wealth of details about normal cellular processes involving the ESCRT proteins, including vesicle budding into endosomal compartments called multi-vesicular bodies (MVB) [3] and the later discovery of the involvement of this process in the terminal events of cell division and cell separation [4]
Summary
The late Nobel Laureate Sir Peter Medawar once memorably described viruses as ‘bad news wrapped in protein’. Gag binds to a dimeric genomic RNA via its NC domain to form ribonucleoprotein complex which is trafficked to the membrane where more Gag assembles and budding occurs (black dashed-box and B). It has been suggested in HIV that NEDD-like ligase either ubiquitinates and activates ESCRT-I [69], or interacts with ALIX to function in virus release [70].
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