Proteins, nucleic acids and lipids: A coordinated effort for the production of infectious virions during HIV assembly

Abstract

Human immunodeficiency virus (HIV) is an enveloped RNA virus belonging to the lentivirus genus of retroviruses. Like other type-C retroviruses, HIV assembly and budding occur concurrently at the plasma membrane of infected cells. Consequently the formation of HIV virus particles requires that the key structural components of the virus, and the viral genomic RNA, are brought together at the cellular membrane where new particles are assembled. The formation of infectious HIV viral particles is driven principally by the HIV Gag poly-precursor protein via a complex series of steps requiring multiple viral-host interactions. During HIV assembly, Gag utilizes cellular machineries within the host cell, such as the endosomal sorting pathway to facilitate viral assembly and release, the requirement for which is conserved within the retrovirus family as well as many other enveloped virus families. The HIV Gag polyprotein, which encodes the major structural components of the virus, also interacts with a second viral precursor protein, GagPol, which encodes the viral enzymes and is responsible for the targeting of these proteins to the site of virion assembly via interactions with specific lipids within the plasma membrane. The interaction between Gag and GagPol also functions to facilitate the selection and packaging of viral genomic RNA and primer tRNAs, where Gag has the capacity to identify these specific RNA species from a large background population of cytoplasmic host cell RNAs, non-genomic spliced viral RNAs, and hundreds of other tRNA species. HIV assembly and budding are believed to take place at specific microdomains within the plasma membrane which are enriched in cholesterol and sphingolipids. This results in virion particles with a unique lipid membrane composition which is critical for HIV infectivity. The overall objective of this chapter is to discuss how these various virion-associated components and their interactions coordinate the assembly, release, and propagation of HIV.