Translational control by viral proteinases

Abstract

Most RNA viruses have evolved strategies to regulate cellular translation in order to promote preferential expression of the viral genome. Positive strand RNA viruses express large portions, or all of their proteome via translation of large polyproteins that are processed by embedded viral proteinases or host proteinases. Several of these viral proteinases are known to interact with host proteins, particularly with the host translation machinery, and thus, encompass the dual functions of processing of viral polyproteins and exerting translation control. Picornaviruses are perhaps the best characterized in regards to interaction of their proteinases with the host translation machinery and will be emphasized here. However, new findings have shown that similar paradigms exist in other viral systems which will be discussed.

mRNA Decapping Enzyme 1a (Dcp1a)-induced Translational Arrest through Protein Kinase R (PKR) Activation Requires the N-terminal Enabled Vasodilator-stimulated Protein Homology 1 (EVH1) Domain

“…Poliovirus proteases tend to selectively target proteins involved in cellular gene expression or the antiviral response to make the cellular environment more amenable to viral replication (68). Although Dcp1a has a described role in RNA degradation, no form of poliovirus RNA contains a 5Ј-methylguanosine cap, and it was not expected to be targeted by Dcp1a for decapping reactions.…”

Inhibition of U snRNP assembly by a virus-encoded proteinase

“…For example, the virus inhibits host transcription through proteolysis of factors that aid in transcription by RNA polymerases I, II, and III, such as the TATA-box-binding and CRE-binding proteins (for review, see Weidman et al 2001). Similarly, several translation initiation factors are proteolyzed by virus-encoded proteinases, resulting in the inhibition of cap-dependent host mRNA translation while allowing the cap-independent translation of the viral polypeptide mediated by an internal ribosome entry sequence (for review, see Lloyd 2006). Given these precedents for destruction of specific host proteins during viral infection, we hypothesized that the reduction in Sm core assembly observed in poliovirus-infected extracts could be due to destruction of a specific component of the assembly machinery.…”

“…S4). Poliovirus encodes two proteinases, 2A pro and 3C pro , known to specifically target certain host proteins (for review, see Lloyd 2006). Studies have defined specific consensus cleavage motifs for the 2A and 3C proteinases (Sommergruber et al 1992(Sommergruber et al , 1994Lamphear et al 1993;Tong 2002).…”

Le profilage ribosomique

“…Certains virus vont par exemple cibler les zones conservées des ARNm cellulaires pour empêcher leur traduction. C'est le cas des poxvirus qui expriment des enzymes de dégradation de la coiffe permettant de réduire le pool d'ARNm traduits selon la voie coiffe-dépendante ( Figure 3B) [22]. D'autres virus, comme les picornavirus et les rétrovirus, vont quant à eux cibler des facteurs essentiels pour l'initiation de la traduction coiffe-dépendante, tels que eIF4G et PABP (poly(A)-binding protein), et induire leur dégradation ( Figure 3B) [18].…”