Dengue virus RNA structure specialization facilitates host adaptation

VILLORDO SM.; FILOMATORI CV. ; SÁNCHEZ-VARGAS I. ; BLAIR CD.; GAMARNIK A.

PLOS PATHOGENS

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015

1553-7366

Many viral pathogens cycle between humans and insects.These viruses must have evolved strategies for rapid adaptation to differenthost environments. However, the mechanistic basis for the adaptation processremains poorly understood. To study the mosquito-human adaptation cycle, weexamined changes in RNA structures of the dengue virus genome during hostadaptation. Deep sequencing and RNA structure analysis, together with fitnessevaluation, revealed a process of host specialization of RNA elements of theviral 3?UTR. Adaptation to mosquito or mammalian cells involved selection of differentviral populations harvesting mutations in a single stem-loop structure. The host specialization of the identified RNAstructure resulted in a significant viral fitness cost in the non-specializedhost, posing a constraint during host switching.  Sequence conservation analysis indicated thatthe identified host adaptable stem loop structure is duplicated in dengue andother mosquito-borne viruses. Interestingly, functional studies usingrecombinant viruses with single or double stem loops revealed that duplicationof the RNA structure allows the virus to accommodate mutations beneficial inone host and deleterious in the other.  Our findings reveal new conceptsin adaptation of RNA viruses, in which host specialization of RNA structures resultsin high fitness in the adapted host, while RNA duplication confers robustnessduring host switching.