Enhancement of dengue virus translation: role of the 3′ untranslated region and the terminal 3′ stem-loop domain

An essential step for a productive infection by the dengue flavivirus (DEN) is translation of the m 7G-capped, nonpolyadenylated positive-sense RNA genome. We have recently identified sequences within the DEN 3′ untranslated region (UTR) that modulate viral translation. Here, we show that the DEN type 2 (DEN2) 3′UTR stimulated translation of m 7G-capped DEN2 5′UTR-containing reporter mRNAs in baby hamster kidney (BHK) cells compared to a 3′ vector sequence. Analogous to the 3′ poly(A) tail, the DEN2 3′UTR also enhanced translation of reporter mRNAs containing (i) a nonfunctional A cap, (ii) the 5′UTR of human β-globin, or (iii) a viral internal ribosome entry site (IRES). In all cases, approximately half of the translation efficiency was due to the terminal 3′ stem-loop (3′SL) domain. In addition, the 3′SL domain increased the association of mRNAs with polysomes. Together, these results indicate that the DEN2 3′UTR, mediated in part by the 3′SL domain, enhances translation initiation, possibly after recognition of the 5′ cap structure.