Abstract
The translation of enterovirus 71 (EV71) is mediated by an internal ribosome entry site (IRES)-dependent manner. EV71 IRES comprises five highly structured domains (domains II-VI) in the 5′-untranslated region of the viral mRNA. A conserved AUG triplet residing in domain VI is proposed to be the ribosome entry site. It is thus envisaged that the highly structured conformation of domain VI may actually reduce the accessibility of the AUG triplet to the ribosome. This study identified a DEAD-box family RNA helicase, DDX3X, that positively regulated the EV71 IRES-dependent translation. The helicase activity of DDX3X was required for the stimulation of EV71 IRES activity; however, DDX3X was no longer important for the IRES activity when the secondary structure of domain VI was destabilized. DDX3X interacted with the truncated eIF4G which bound specifically to domain V. Thus, we proposed that DDX3X might bind to domain VI or a region nearby via the interaction with the truncated eIF4G, and subsequently unwound the secondary structure of domain VI to facilitate ribosome entry. Additionally, we demonstrated that the viral 2Apro and 3Cpro enhanced the IRES-dependent translation via their protease activities. Together, these results indicate that DDX3X is an important RNA helicase involved in EV71 IRES-dependent translation and that IRES translation is enhanced by viral infection, partly mediated by viral protease activity.
Highlights
Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease (HFMD) mainly in infants and young children
We further investigated the role of DDX3X in the enterovirus 71 (EV71) replication cycle
These results suggest that DDX3X may act as a positive regulator of EV71 replication
Summary
Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease (HFMD) mainly in infants and young children. EV71 infection is self-limiting, but occasionally it causes neurological complications, such as encephalitis, aseptic meningitis, and acute flaccid paralysis, or can even lead to death (McMinn, 2002). The EV71 genome encodes a large polyprotein that is further processed into 11 structural and non-structural proteins. The 5 -untranslated region (5 -UTR) of EV71 is approximately 750 nucleotides (nt) that contains a cloverleaf structure and an internal ribosome entry site (IRES). The cloverleaf structure (domain I) is an important cis-element for viral RNA replication (Barton et al, 2001; Lyons et al, 2001), and the IRES element
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.