Residue 627 of PB2 is a determinant of cold sensitivity in RNA replicationof avian influenza viruses

Human influenza A viruses replicate in the upper respiratory tract at a tem perature of about 33 degreesC, whereas avian viruses replicate in the intes tinal tract at a temperature close to 41 degreesC. In the present study, we analyzed the influence of low temperature (33 degreesC) on RNA replication of avian and human viruses in cultured cells. The kinetics of replication of the NP segment were similar at 33 and 37 degreesC for the human A/Puerto -Rico/8/34 and A/Sydney/5/97 viruses, whereas replication was delayed at 33 degreesC compared to 37 degreesC for the avian A/FPV/Rostock/ 34 and A/Mal lard/NY/6750/78 viruses. Making use of a genetic system for the in vivo rec onstitution of functional ribonucleoproteins, we observed that the polymera se complexes derived from avian viruses but not human viruses exhibited col d sensitivity in mammalian cells, which was determined mostly by residue 62 7 of PB2, Our results suggest that a reduced ability of the polymerase comp lex of avian viruses to ensure replication of the viral genome at 33 degree sC could contribute to their inability to grow efficiently in humans.