Translation initiation of viral mRNAs

Abstract

Viruses depend on cells for their replication but have evolved mechanisms to achieve this in an efficient and, in some instances, a cell-type-specific manner. The expression of viral proteins is frequently subject to translational control. The dominant target of such control is the initiation step of protein synthesis. Indeed, during the early stages of infection, viral mRNAs must compete with their host counterparts for the protein synthetic machinery, especially for the limited pool of eukaryotic translation initiation factors (eIFs) that mediate the recruitment of ribosomes to both viral and cellular mRNAs. To circumvent this competition viruses use diverse strategies so that ribosomes can be recruited selectively to viral mRNAs. In this review we focus on the initiation of protein synthesis and outline some of the strategies used by viruses to ensure efficient translation initiation of their mRNAs.

Translation initiation of the HIV-1 mRNA

“…Success in this competition will ensure the reprogramming of the host machinery toward the production of virally encoded proteins and, ultimately, the release of infectious virions. 132,133 In the case of the HIV-1, the 5 0 UTR has been shown to drive cap-dependent translation initiation under normal physiological conditions 33,51 and to mediate IRES-dependent protein synthesis during stress conditions known to hinder cap-dependent translation initiation. 32,86,88,91,118 Interestingly, in the course of viral replication, HIV-1 has been shown to change cellular homeostasis altering several components of the host translational apparatus which results in the inhibition of cap-dependent translation.…”

Picornavirus IRES elements: RNA structure and host protein interactions

“…Viral IRES are characterized by the presence of ignored AUGs upstream of the functional start codon, heavy RNA structure and high GC content (Balvay et al, 2009;Lopez-Lastra et al, 2010;Martinez-Salas, 2008;Plank and Kieft, 2012). Yet, despite performing the same function, IRES elements differ in nucleotide sequence, RNA secondary structure and trans-acting factors requirement.…”

The 5′ Untranslated Region of the Human T-Cell Lymphotropic Virus Type 1 mRNA Enables Cap-Independent Translation Initiation

“…Functionally, IRESs were identified by inserting the poliovirus (PV) or encephalomyocarditis virus (EMCV) 5=UTR into the intercistronic spacer of a bicistronic construct encoding two proteins (3,4). Expression of the second cistron was dependent upon the ability of the inserted sequence to promote internal ribosome binding and translation independent of the first cistron (5)(6)(7). In general, IRES-mediated translation is independent of the nature of the extreme 5= end of the RNA since it does not require the 5=cap structure to be functional.…”

“…In general, IRES-mediated translation is independent of the nature of the extreme 5= end of the RNA since it does not require the 5=cap structure to be functional. In the artificial bicistronic mRNA model, translation of the downstream cistron occurs even when translation of the upstream cistron is abolished (5)(6)(7). The mRNAs of many viruses from other families, including several members of the Retroviridae family, have been shown to also initiate translation via an IRES (6,8).…”

“…In the artificial bicistronic mRNA model, translation of the downstream cistron occurs even when translation of the upstream cistron is abolished (5)(6)(7). The mRNAs of many viruses from other families, including several members of the Retroviridae family, have been shown to also initiate translation via an IRES (6,8). Identification of IRESs within retroviruses has been the subject of intense debates over the past several years (8,9).…”