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Journal of Virology, June 2001, p. 5398-5404, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5398-5404.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Residue 627 of PB2 Is a Determinant of Cold Sensitivity in RNA Replication of Avian Influenza Viruses

Pascale Massin, Sylvie van der Werf,* and Nadia Naffakh

Unité de Génétique Moléculaire des Virus Respiratoires, URA CNRS 1966, Institut Pasteur, Paris, France

Received 25 September 2000/Accepted 21 February 2001

Human influenza A viruses replicate in the upper respiratory tract at a temperature of about 33°C, whereas avian viruses replicate in the intestinal tract at a temperature close to 41°C. In the present study, we analyzed the influence of low temperature (33°C) 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°C for the human A/Puerto-Rico/8/34 and A/Sydney/5/97 viruses, whereas replication was delayed at 33°C compared to 37°C for the avian A/FPV/Rostock/34 and A/Mallard/NY/6750/78 viruses. Making use of a genetic system for the in vivo reconstitution of functional ribonucleoproteins, we observed that the polymerase complexes derived from avian viruses but not human viruses exhibited cold sensitivity in mammalian cells, which was determined mostly by residue 627 of PB2. 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.

* Corresponding author. Mailing address: Unité de Génétique Moléculaire des Virus Respiratoires, URA CNRS 1966, Institut Pasteur, 25, rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33-1-45-68-87-22. Fax: 33-1-40-61-32-41. E-mail: svdwerf{at}pasteur.fr.

Journal of Virology, June 2001, p. 5398-5404, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5398-5404.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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