The role of nucleoprotein in transcription and replication of the influenza A virus genome

• Main Author: Turrell, Lauren
• Other Authors: Fodor, Ervin ; Vreede, Frank
• Published: University of Oxford 2015
• Subjects: 572
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.719873

The eight vRNA genome segments of influenza A virus are bound by the viral RNA polymerase at the 5' and 3' ends, and associated with oligomeric nucleoprotein (NP) to form viral ribonucleoprotein (vRNP) complexes. These vRNP complexes carry out both viral transcription and replication within the nucleus of the host cell. The role of NP in viral transcription and replication, although essential, is not well understood. The findings presented in this thesis support a role for NP in the elongation phase of viral transcription and replication, but suggest that NP does not play a role in the regulation of initiation or termination of replication and transcription by the viral RNA polymerase. For NP to support elongation, it has to be recruited onto the viral RNA and oligomerise, to form a RNP complex. NP is likely to exist in a monomeric state, in the infected cell, prior to being recruited into the vRNP. The data presented here demonstrates that NP recruitment onto the viral RNA is mediated through NP-NP homooligomerisation and that oligomerisation of NP, within the infected cell, is regulated by reversible phosphorylation within the oligomerisation domain. In addition to this, compatibility between NP and the viral polymerase is essential for NP to support RNA polymerase activity. The N-terminus of NP is not required for this compatibility; however, evidence points towards loops within NP, responsible for RNA and polymerase binding, playing a role in the interplay between the RNA polymerase and NP within the RNP complex. Overall, this work provides new mechanistic insights into the assembly and regulation of viral RNP complexes.