Cooperation between the hemagglutinin of avian viruses and the matrix protein of human influenza A viruses.
To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant human viruses and amantadine-sensitive avian strains. By using antisera against the human virus HAs and amantadine, we selected reassortants containing the human virus M gene and the avian virus HA gene. In our system, high virus yields and large, well-defined plaques indicated that the avian HAs and the human M gene products could cooperate effectively; low virus yields and small, turbid plaques indicated that cooperation was poor. The M gene products are among the primary components that determine the species specificities of influenza A viruses. Therefore, our system also indicated whether the avian HA genes effectively reassorted into the genome and replaced the HA gene of the prevailing human influenza A viruses. Most of the avian HAs that we tested efficiently cooperated with the M gene products of the early human A/PR/8/34 (H1N1) virus; however, the avian HAs did not effectively cooperate with the most recently isolated human virus that we tested, A/Nanchang/933/95 (H3N2). Cooperation between the avian HAs and the M proteins of the human A/Singapore/57 (H2N2) virus was moderate. These results suggest that the currently prevailing human influenza A viruses might have lost their ability to undergo antigenic shift and therefore are unable to form new pandemic viruses that contain an avian HA, a finding that is of great interest for pandemic planning.
Scholtissek
Christoph
C
Department of Virology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
Stech
Jürgen
J
Krauss
Scott
S
Webster
Robert G
RG
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D024882:Drug Resistance, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000821:virology; D007668:Kidney / Q000166:cytology / Q000821:virology; D011200:Poultry; D016865:Reassortant Viruses; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014763:Viral Matrix Proteins; C109963:hemagglutinin, avian influenza A virus; D000547:Amantadine