High prevalence of amantadine resistance among circulating European porcine influenza A viruses.
Genetic analysis of the M2 sequence of European porcine influenza A viruses reveals a high prevalence of amantadine resistance due to the substitution of serine 31 by asparagine in all three circulating subtypes, H1N1, H3N2 and H1N2. The M segment of all resistant strains belongs to a single genetic lineage. Whereas the first amantadine-resistant porcine strain was isolated in 1989, isolation of the last amantadine-susceptible strain dates to 1987, suggesting a displacement of amantadine-susceptible viruses by resistant strains soon after emergence of the mutation. Analysis of natural selection by codon-based tests indicates negative selection of codons 30, 31 and 34 which confer amantadine resistance. The codons 2, 11-28 and 54 of porcine and human strains exhibit differences in the patterns of substitution rates, suggesting different selection modes. Transfer of amantadine resistance by exchange of the M segment and viability of recombinant A/WSN/33 viruses with avian-like M segments raises concerns about the emergence of natural human reassortants.
Krumbholz
Andi
A
Institut für Virologie und Antivirale Therapie, Universitätsklinikum Jena, Hans Knöll Str. 2, D-07745 Jena, Germany.
Schmidtke
Michaela
M
Institut für Virologie und Antivirale Therapie, Universitätsklinikum Jena, Hans Knöll Str. 2, D-07745 Jena, Germany.
Bergmann
Silke
S
Institut für Virologie und Antivirale Therapie, Universitätsklinikum Jena, Hans Knöll Str. 2, D-07745 Jena, Germany.
Motzke
Susann
S
Institut für Virologie und Antivirale Therapie, Universitätsklinikum Jena, Hans Knöll Str. 2, D-07745 Jena, Germany.
Bauer
Katja
K
Institut für Virologie und Antivirale Therapie, Universitätsklinikum Jena, Hans Knöll Str. 2, D-07745 Jena, Germany.
Stech
Jürgen
J
Friedrich Loeffler Institute, Federal Research Institute for Animal Health, Institute of Molecular Biology, Südufer 10, D-17493 Greifswald - Insel Riems, Germany.
Dürrwald
Ralf
R
IDT Biologika GmbH, Bereich Forschung und Entwicklung, Am Pharmapark, D-06861 Dessau-Rosslau, Germany.
Wutzler
Peter
P
Institut für Virologie und Antivirale Therapie, Universitätsklinikum Jena, Hans Knöll Str. 2, D-07745 Jena, Germany.
Zell
Roland
R
Institut für Virologie und Antivirale Therapie, Universitätsklinikum Jena, Hans Knöll Str. 2, D-07745 Jena, Germany.
D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral; D005060:Europe / Q000453:epidemiology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D009980:Influenza A virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000453:epidemiology / Q000662:veterinary* / Q000821:virology; D010802:Phylogeny; D012367:RNA, Viral / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D013552:Swine; D013553:Swine Diseases / Q000453:epidemiology* / Q000821:virology
D000998:Antiviral Agents; D012367:RNA, Viral; D000547:Amantadine