Comparative Analysis of Gammaherpesvirus Circular RNA Repertoires: Conserved and Unique Viral Circular RNAs

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Abstract
Infection with oncogenic gammaherpesviruses leads to long-term viral persistence through a dynamic interplay between the virus and the host immune system. Critical for remodeling of the host cell environment after the immune responses are viral noncoding RNAs that modulate host signaling pathways without attracting adaptive immune recognition. Despite the importance of noncoding RNAs in persistent infection, the circRNA class of noncoding RNAs has only recently been identified in gammaherpesviruses. Accordingly, their roles in virus infection and associated oncogenesis are unknown. Here we report evolutionary conservation of EBV-encoded circRNAs determined by assessing the circRNAome in rLCV-infected lymphomas from an SIV-infected rhesus macaque, and we report latent and lytic circRNAs from KSHV and MHV68. These experiments demonstrate utilization of the circular RNA class of RNAs across 4 members of the gammaherpesvirus subfamily, and they identify orthologues and potential homoplastic circRNAs, implying conserved circRNA functions in virus biology and associated malignancies.
Funding Information
  • National Institutes of Health (R01AI101046, R01AI106676)
  • Department of Defense (W81XWH-16-1-0318)
  • Department of Defense (W81XWH-16-1-0317)
  • HHS | National Institutes of Health (R01CA188609)
  • HHS | National Institutes of Health (R00GM112877)
  • HHS | National Institutes of Health (R01AI108407)
  • HHS | National Institutes of Health (R01CA119917)
  • HHS | National Institutes of Health (P01CA214091)

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