Jude Martin
School of Life Sciences
Increasing the mutation frequency of VEE virus strain TC-83 modulates the RNAi response in Aedes cell lines producing an increased piRNA response in siRNA-deficient cells
TC-83 is the vaccine strain of Venezuelan Equine Encephalitis Virus ( VEEV ). A well characterized RNA-dependent RNA-polymerase ( RdRp ) mutant , TC-83 _ 3X , exhibits increased mutational frequency which results in attenuation during in vivo infection . To test whether this change in mutation frequency results in changes in the RNAi response that is the primary antiviral response in mosquito cells , U4.4 and C7 / 10 cells , effective and defective in the siRNA response respectively , were infected with TC-83 _ 3X and the cellular RNAi reads sequenced . The results show that in U4.4 cells that have an effective siRNA response pathway , no significant siRNA response is identified upon infection with TC-83 _ 3X . Interestingly , in C7 / 10 cells , activation of the piRNA response was observed . This was indicated by the increase of RNA reads of 24-31nt showing U1 and A10 bias , which are characteristics of the piRNA response . This suggests that the piRNA response is active against TC-83 _ 3X when the siRNA response is defective , while the increased diversity of the TC-83 _ 3X virus eliminates the effectiveness of the siRNA response in U4.4 cells . In a broader sense this indicates that alterations to frequency of mutation within an RNA virus may result in significant changes in host-cell interactions .
Postgraduate Conference 2021 Page 30