Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses

In order to determine how efficiently the polymerase proteins derived from human and avian influenza A viruses can interact with each other in the con text of a mammalian cell, a genetic system that allows the in vivo reconsti tution of active ribonucleoproteins was used, The ability to achieve replic ation of a viral-like reporter RNA in COS-1 cells was examined with heteros pecific mixtures of the core proteins (PB1, PB2, PA and NP) from two strain s of human viruses (A/Puerto Rico/8/34 and A/Victoria/3/75), two strains of avian viruses (A/Mallard/NY/6750/78 and A/FPV/Rostock/34), and a strain of avian origin (A/Hong Kong/156/97) that was isolated from the first human c ase of H5N1 influenza in Hong Kong in 1997, In accordance with published ob servations on reassortant viruses, PB2 amino acid 627 was identified as a m ajor determinant of the replication efficiency of heterospecific complexes in COS-1 cells, Moreover, the results showed that replication of the viral- like reporter RNA was more efficient when PB2 and NP were both derived from the same avian or human virus or when PB1 was derived from an avian virus, whatever the origin of the other proteins, Furthermore, the PB1 and PB2 pr oteins from the A/Hong-Kong/156/97 virus exhibited intermediate properties with respect to the corresponding proteins from avian or human influenza vi ruses, suggesting that some molecular characteristics of PB1 and PB2 protei ns might at least partially account for the ability of the A/Hong Kong/156/ 97 virus to replicate in humans.