Switch from Cap- to Factorless IRES-Dependent 0 and +1 Frame Translation during Cellular Stress and Dicistrovirus Infection

Wang, Qing S.; Jan, Eric

The IGR IRESs can be classified into two types. Type I and II IGR IRESs are exemplified by the CrPV and IAPV IGR IRES, respectively ( Figure 1B ). Type II IRESs contain an extra stem loop (SLIII) within the PKI domain and a longer L1.1 region ( Figure 1B) . We previously showed that the PKI domains can be swapped between Type I and II IGR IRESs without compromising function [23] . Within the Type II IGR IRESs, the honey bee viruses also contain an extra 14-18 bp stem loop (SLVI), which enhances IGR IRES translation in vitro [24] [25] [26] . Recently, we demonstrated that a subset of Type II IGR IRESs that include the honey bee virus, IAPV, can direct translation in both the 0 and +1 frames to synthesize the viral structural proteins and a hidden +1 frame protein, called ORFx [25] . An U-G base pair (U6562/ G6618) adjacent to the PKI domain is necessary to shift the reading frame of the ribosome into the +1 frame in vitro ( Figure 1B ) [25] . ORFx is expressed in virally-infected honey bees suggesting that its expression is important for viral infection [25] . However, the role of ORFx is currently not known. Furthermore, it has not been investigated whether +1 frame translation directed by the IGR IRES is regulated distinctly of 0 frame translation.