Characterizing the effects of differentially adapted influenza PB2 proteins on duck MAVS-mediated interferon beta signaling

• Author / Creator

  Tetrault, David G

• The influenza A viral RNA polymerase is responsible for viral replication and greatly affects influenza A virus (IAV) virulence and host range. The PB2 influenza polymerase subunit is the primary polymerase determinant of influenza host range and virulence. It was previously shown that PB2 interacts with and inhibits MAVS-mediated interferon-β (IFN-β) expression to differing degrees depending on the localization of PB2 within mammalian cells. Specifically, mammalian adapted PB2 localized to the mitochondria while avian strains do not. This difference in localization was shown to be determined by a single amino acid difference in PB2. Here, I helped elucidate, in collaboration with the Sun Hur research group, the mechanism by which RIG-I activates MAVS-mediated IFN- β signaling. I subsequently determined that the PB2 proteins from 2 mammalian and 4 avian IAV strains differ in their abilities to inhibit duck MAVS-mediated IFN-β signaling in avian cells. Contrary to what was expected, mammalian adapted PB2 remained a potent inhibitor of avian IFN-β signaling despite major differences between human and duck MAVS. Additionally, swapping the adaptive PB2 residue 9, between avian and human adapted IAV strains, did not affect the general pattern of PB2-mediated IFN-β inhibition. Although, changes in PB2-MAVS interactions and PB2 localization were observed. My results demonstrate that the PB2 inhibition of IFN-β in avian cells is partially dependent on PB2-MAVS interactions and PB2 localization. Together, these findings suggest mammalian IAV PB2 proteins have acquired a cross species ability to inhibit IFN-β signaling, which has the potential to affect both IAV virulence and fitness.

• Subjects / Keywords

  • Influenza
  • MAVS
  • Interferon
  • PB2

• Graduation date

  Fall 2015

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3DV1D32V

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.