Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells.

Karine Labadie (1) , Emmanuel dos Santos Afonso (1) , Marie-Anne Rameix-Welti (1) , Sylvie van Der Werf (1) , Nadia Naffakh (1)

1 Génétique Moléculaire des Virus Respiratoires

The transcription/replication activity of ribonucleoproteins derived from influenza A primary isolates of human (A/Paris/908/97) or avian origin (A/Mallard/Marquenterre/MZ237/83, A/Hong Kong/156/97) was compared upon reconstitution in mammalian or avian cells, using viral-like reporter RNAs synthesized under the control of the human and chicken RNA polymerase I promoters, respectively. In avian cells, transcription/replication activities were in the same range with all ribonucleoproteins tested. In human cells, ribonucleoproteins derived from A/Mallard/Marquenterre/MZ237/83 showed reduced transcription/replication activity and reduced NP binding to the PB1-PB2-PA complex (P) or to the isolated PB2 subunit, as compared to the ribonucleoproteins derived from A/Paris/908/97. Both defects were restored when PB2 residue Glu-627 was changed to a Lys. Ribonucleoproteins derived from the human A/Hong Kong/156/97 H5N1 isolate showed efficient NP-P interaction in human cells, and high levels of activity which were determined mostly by the PB2 and PA proteins. Our data suggest that PB2 might play a pivotal role in molecular interactions involving both the viral nucleoprotein and cellular proteins.

Domaines: Virologie

Karine Labadie, Emmanuel dos Santos Afonso, Marie-Anne Rameix-Welti, Sylvie van Der Werf, Nadia Naffakh. Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells.. Virology, 2007, 362 (2), pp.271-82. ⟨10.1016/j.virol.2006.12.027⟩. ⟨hal-00167811⟩