Flavivirus 3' Untraslated Regions: structural analysis, host adaptation and viral fitness

FILOMATORI, C. V.; FERNANDEZ-SESMA, A.; VILLORDO, S. M.; PALLARES, H.M.; CARBALLEDA J. M.; GEBHARD, L.; GAMARNIK, A. V.

San José

Workshop; V ICGEB Workshop on Human RNA Viruses; 2016

ICGEB

p { margin-bottom: 0.25cm; direction: ltr; color: rgb(0, 0, 10); line-height: 120%; text-align: left; }p.western { font-family: "Calibri",serif; font-size: 11pt; }p.cjk { font-family: "Droid Sans Fallback"; font-size: 11pt; }p.ctl { font-size: 11pt; }Flavivirusesinclude a highly diverse group of arboviruses with a globaldistribution and a high human disease burden. Most flaviviruses cyclebetween insects and vertebrate hosts. In addition to coding for viralproteins, the viral genome contains signals in RNA structures thatgovern the amplification of viral components and participate intriggering or evading antiviral responses. In this work, we analyzedRNA structures present in the 3?UTR of flavivirus genomesassociated to host adaptation.Usingconservation patterns, prediction algorithms and experimental data,we proposed models for the 3' UTR of different groups offlaviviruses. Flaviviruses can be divided into four large ecologicalgroups: the Mosquito Borne group (MBFV), the Tick Borne group (TBFV),the vertebrate specific flavivirus group, also named No Known Vectorflaviruses (NKFV), and the ones that have been only isolated frominsects known as Insect Specific Flaviviruses (ISFV). Most MBFV3?UTRs display two pairs of duplicated RNA structures named StemLoops (SLs) and Dumbbell (DBs). The TBFV group shows sizeheterogeneity containing group-specific RNA structure duplicationswith conserved structural blocks. The NKFV group contains singlecopies of conserved RNA structures, and the ISFV contains shortsequence repeats withlow potential for high order RNAstructures. The analysis indicates the presence of complex RNAstructure duplications in the 3' UTR of most vector-borneflaviviruses.Experimentalhost adaptation studies using dengue virus (DENV) indicates thatinstead of redundant functions, each duplicated RNA element plays adistinct role in mosquito or human infected cells. Interestingly,host adaptable RNA structures present at the 3?UTR are alsoassociated to the production of subgenomic flavivirus RNAs (sfRNAs).Thus, we investigated the link between host adaptation and sfRNAproduction, and found that defined patterns of sfRNAs are alsoassociated to different viral fitness in each host.