Translational control of retroviruses

Key Points The retroviral family is described, and an overview of the retroviral life cycle, the genetic organization and a brief description of the process of translation initiation in Eucaryotes is provided. The role of viral RNA structures on translation initiation is discussed. IRES elements characterized in HIV-1, HIV-2 and SIV, and those which are located both within the 5′-UTR and the Gag coding region, are responsible for the synthesis of the N-truncated shorter Gag isoforms. Short upstream reading frames regulate translation initiation in avian simple retroviruses such as Rous sarcoma virus (RSV). RNA translational enhancing elements that have been described in Mason-Pfizer monkey virus (M-PMV) and the avian spleen necrosis virus (SNV) are discussed. The interaction between the TAR RNA structure and the Tat protein also has a significant regulatory role in translation that is mainly exerted through the PKR pathway. The interaction of Rev with the RNA responsive element was shown to enhance Gag production by a mechanism that is not due to an increase of genomic RNA export, but is rather due to an enhanced recruitment of this genomic RNA into polyribosomes. The viral protease of a large number of retroviruses including MLV, HIV-1, HIV-2 and SIV can induce the cleavage of the initiation factor eIF4GI, which is an essential component of the host translational apparatus. Such a proteolytic event was shown to strongly inhibit ribosomal scanning. Retroviruses are a unique family of RNA viruses that depend on the translational machinery of the host cell for protein synthesis. Here, the mechanisms used by these viruses to ensure efficient protein synthesis within a highly competitive cellular environment are reviewed. All replication-competent retroviruses contain three main reading frames, gag , pol and env , which are used for the synthesis of structural proteins, enzymes and envelope proteins respectively. Complex retroviruses, such as lentiviruses, also code for regulatory and accessory proteins that have essential roles in viral replication. The concerted expression of these genes ensures the efficient polypeptide production required for the assembly and release of new infectious progeny virions. Retroviral protein synthesis takes place in the cytoplasm and depends exclusively on the translational machinery of the host infected cell. Therefore, not surprisingly, retroviruses have developed RNA structures and strategies to promote robust and efficient