Trafficking of HIV-1 RNA: Recent Progress Involving Host Cell RNABinding Proteins

Andrew   J.   Mouland; Eric   A.   Cohen; Luc      DesGroseillers

doi:10.2174/1389202033490402

Abstract

RNA trafficking within the cell represents an important component of gene expression in a variety of organisms. This process directs RNA to select regions of the cell and has functional consequences to cell physiology and function. Intranuclear RNA trafficking can also influence RNA maturation including 5- and 3-end-processing, splicing and nuclear export. Within the cytosol, RNA trafficking influences the localization and levels of gene expression of the protein product to prevent ectopic expression, for example. For most cellular RNAs this process usually depends on an accurate and precisely timed sequence of events where each step depends on that which precedes it, usually initiated by the specific binding of trans-acting proteins to cognate RNA cis sequences to dictate their fate. This is also true for retroviral RNAs (see below). Human immunodeficiency virus type 1 (HIV-1) is a major affliction of the 21st century and it is estimated that more than 45 million people worldwide are infected. Although no cure is available, regimented antiviral drug therapy has become the golden standard for care. Accompanied with lifestyle changes both can not only bring virus to near undetectable levels but can also dramatically increase the lifespan and maintain a quality of life for a person living with the virus. As an intracellular parasite HIV-1 uses host cell proteins and machinery in most -if not all- of its replication steps including viral entry, integration, transcription and viral assembly. The understanding of their involvement in these steps will contribute in the treatment and perhaps the eventual eradication of HIV-1 infection. For this -the next generation of HIV-1 therapeutics- we will require a profound understanding of the biological role of these factors and, specifically, how they interact with the virus. This information will eventually lead to the development of specific inhibitors, which will likely be used in combination with existing retroviral therapeutic approaches. This review serves to update the reader on particular aspects of nucleocytoplasmic trafficking of HIV-1 RNAs involving HIV-1 Rev, Gag and associated host cell co-factors. It will update the reader on the current body of knowledge on host and viral proteins and mechanisms involved in the movement of HIV-1 RNAs out of the nucleus, within the cytosol and eventually to the sites of viral assembly. The novelty will be in its examination of the recent developments that implicate cellular RNA-binding proteins involved in HIV-1 RNA localization and cytosolic RNA trafficking. It is expected that host cell proteins and viral proteins will ultimately prove to be critical for these late steps of the viral lifecycle.

Keywords: hiv-1 rna, rna-binding protein, hiv trafficking, rna trafficking, hiv-1 rev

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