No abstract

During 2013–2014, French Polynesia experienced an outbreak of Zika virus infection. Serosurveys conducted at the end of the outbreak and 18 months later showed lower than expected disease prevalence rates (49%) and asymptomatic:symptomatic case ratios (1:1) in the general population but significantly different prevalence rates (66%) and asymptomatic:symptomatic ratios (1:2) in schoolchildren.

These results corroborate the expected high transmission of DENV and conversely suggest that no active circulation of ZIKV, JEV, and WNV occurred in French Polynesia before 2011. Information provided by this study may be useful for public health authorities to improve surveillance and implement strategies to prevent the transmission of arboviruses.

Efficient translation of most eukaryotic mRNAs results from synergistic cooperation between the 5 m 7 GpppN cap and the 3 poly(A) tail. In contrast to such mRNAs, the polyadenylated genomic RNAs of picornaviruses are not capped, and translation is initiated internally, driven by an extensive sequence termed IRES (for internal ribosome entry segment). Here we have used our recently described poly(A)-dependent rabbit reticulocyte lysate cell-free translation system to study the role of mRNA polyadenylation in IRESdriven translation. Polyadenylation significantly stimulated translation driven by representatives of each of the three types of picornaviral IRES (poliovirus, encephalomyocarditis virus, and hepatitis A virus, respectively). This did not result from a poly(A)-dependent alteration of mRNA stability in our in vitro translation system but was very sensitive to salt concentration. Disruption of the eukaryotic initiation factor 4G-poly(A) binding protein (eIF4G-PABP) interaction or cleavage of eIF4G abolished or severely reduced poly(A) tail-mediated stimulation of picornavirus IRES-driven translation. In contrast, translation driven by the flaviviral hepatitis C virus (HCV) IRES was not stimulated by polyadenylation but rather by the authentic viral RNA 3 end: the highly structured X region. X region-mediated stimulation of HCV IRES activity was not affected by disruption of the eIF4G-PABP interaction. These data demonstrate that the protein-protein interactions required for synergistic cooperativity on capped and polyadenylated cellular mRNAs mediate 3-end stimulation of picornaviral IRES activity but not HCV IRES activity. Their implications for the picornavirus infectious cycle and for the increasing number of identified cellular IRES-carrying mRNAs are discussed.The initiation of protein synthesis on most mRNAs in eukaryotes follows binding of the 40S ribosomal subunit near the capped 5Ј end of the mRNA and subsequent migration of this subunit along the mRNA in a 5Ј-to-3Ј direction until a suitable initiation codon is selected (for a review, see reference 29). Recognition of the mRNA 5Ј end and 40S subunit recruitment requires the eukaryotic initiation factor (eIF) 4F complex (for reviews, see references 35 and 43). The eIF4F complex comprises the cap binding protein (eIF4E) and an ATP-dependent RNA helicase (eIF4A) bound, respectively, toward the N and C termini of a scaffold protein, eIF4G (for a review, see references 14 and 35). The C-terminal half of eIF4G is also thought to associate with the multisubunit eIF3 complex, which binds the 40S ribosomal subunit directly thus bridging the gap between the mRNA 5Ј end and the 40S subunit (reviewed in reference 17).The vast majority of eukaryotic mRNAs are not only capped at their 5Ј end but are also polyadenylated at their 3Ј end. Aside from a role in mRNA metabolism (see reference 45 for a review), the poly(A) tail functions as a translational enhancer and interacts synergistically with the 5Ј cap to stimulate translation initiation (12,23,42,43). This co...