Functional study of the Chikungunya Virus 3'UTR in the viral replication cycle in different hosts.

MERWAISS, FERNANDO; SALEH, MARÍA CARLA; FILOMATORI CLAUDIA V.; ALVAREZ, DIEGO E.; BARDOSSY, EUGENIA S.

Conferencia; Viruses and Cells Gordon Research Conference; 2019

Chikungunya virus is a mosquito-borne alphavirusthat after 60 years of exclusive circulation in Asia and Africa has recently spread to Europe and the Americas. Notably, the spread of the virus has been associated to sequence changes in the open reading frame of structural proteins and drastic variations in the 3'UTR that bears conserved sequence repeats that vary in copy number among viral lineages. We and others have previously observed that recombinant chikungunya viruses carrying deletions in the 3'UTR display decreased replication kinetics in mosquito cells, while replication in mammalian cells remains unaffected. We have now combined virus replicons and qPCR assays to assess the role of the 3'UTR sequence repeats on the control of RNA replication, translation and stability in different hosts. To address the significance of sequence repetitions in the spreading of chikungunya infection, we are currently experimentally infecting Aedes albopictus mosquito colonies with virus carrying different 3'UTR sequences. We use virus titration and sequencing of virus RNAs in body, legs and wing, and saliva of infected mosquitoes as a measure of the infection capacity, the dissemination, and the transmission potential of these variants. Our results indicate that viruses carrying an intact 3'UTR outcompete viruses with deletions. We consider that a systematic study of the 3'UTR will provide relevant information that will correlate virus biology and its replicative capacity with still unknown aspects of its pathogenesis and evolution.