Cold-sensitivity of polymerase complexes from human or avian influenza A viruses

Abstract

Background: Human influenza A viruses replicate in the upper respiratory tract at about 33 °C, whereas avian viruses replicate in the intestinal tract at a temperature close to 41 °C. Methods: The influence of low temperature on virus growth and RNA replication of avian and human viruses was analyzed in MDCK cells. The influence of temperature on the functional efficiency of homo- or heterospecific polymerase complexes derived from human or avian viruses, was examined by making use of a genetic system for the in vivo reconstitution of functional ribonucleoproteins. Results: Virus growth, RNA replication kinetics as well as the functional efficiency of the polymerase complex were found to be impaired at 33 °C as compared to 37 °C in the case of the avian A/FPV/Rostock/34 or A/Mallard/NY/6750/78 viruses, whereas they were comparable in the case of the human A/Puerto Rico/8/34 virus. The polymerase complex from the human virus A/Hong Kong/156/97 of avian origin exhibited an intermediate cold-sensitivity. The cold-sensitivity of the complexes of avian origin was determined mostly by residue 627 of PB2. Conclusions: Our results suggest that a reduced ability of the polymerase complex of avian viruses to ensure replication of the viral genome at 33 °C could contribute to their inability to grow efficiently in humans.