Translation control of Enterovirus A71 gene expression

Abstract

Upon EV-A71 infection of a host cell, EV-A71 RNA is translated into a viral polyprotein. Although EV-A71 can use the cellular translation machinery to produce viral proteins, unlike cellular translation, which is capdependent, the viral RNA genome of EV-A71 does not contain a 5′ cap and the translation of EV-A71 protein is cap-independent, which is mediated by the internal ribosomal entry site (IRES) located in the 5′ UTR of EV-A71 mRNA. Like many other eukaryotic viruses, EV-A71 manipulates the host cell translation devices, using an elegant RNA-centric strategy in infected cells. During viral translation, viral RNA plays an important role in controlling the stage of protein synthesis. In addition, due to the cellular defense mechanism, viral replication is limited by down-regulating translation. EV-A71 also utilizes protein factors in the host to overcome antiviral responses or even use them to promote viral translation rather than host cell translation. In this review, we provide an introduction to the known strategies for EV-A71 to exploit cellular translation mechanisms.

Multiple functions of the nonstructural protein 3D in picornavirus infection

“…Picornavirus IRESs evolved to operate in the G 1 phase, a time at which cap-dependent translation is dominant. Upon infection, picornavirus caused inhibition of the cap-dependent translation machinery and utilized host translation machinery for cap-independent translation of viral proteins mediated by its IRES element within the 5′-UTR ( 142 , 147 , 148 ). Studies have shown that 2A pro and 3C pro cleave eukaryotic initiation factor 4G (eIF4G) ( 149 – 151 ), eukaryotic initiation factor 4A (eIF4A) ( 152 ), and eukaryotic initiation factor 5B (eIF5B) ( 153 ), leading to host cell translation shutdown.…”

Enterovirus A71 antivirals: Past, present, and future

“…Like other eukaryotic viruses, EV-A71 hijacks cellular translational machinery to synthesize viral proteins. In contrast to the host cap-dependent cellular translation, the EV-A71 viral genome lacks the 5′ cap, and thus initiates viral RNA translation through an internal ribosomal entry site (IRES)-mediated mechanism that is cap-independent 175 . The IRES is located at the 5′ UTR of EV-A71 mRNA and consists of four domains II to IV.…”

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

“…The IRES is a highly structured region of the viral RNA and interacts with a number of cellular factors. IRES-mediated translation occurs through the combined action of a subset of canonical members of the host translation machinery, and so-called IRES trans-acting factors (ITAFs), which includes the RNA-binding proteins hnRNPA1, PTBP1, PCBP1/2, and FBP1, among others [ 68 , 69 ]. Many of these factors translocate from the nucleus to the cytoplasm during infection and aid in translation initiation by binding to the viral RNA and recruiting ribosomes.…”

“…Many of these factors translocate from the nucleus to the cytoplasm during infection and aid in translation initiation by binding to the viral RNA and recruiting ribosomes. For comprehensive reviews of these ITAFs see references [ 68 , 69 ].…”