J Gen Virol. High prevalence of amantadine resistance among circulating European porcine influenza A viruses.

[Giuseppe]

J Gen Virol. 2009 Feb 17. [Epub ahead of print]

High prevalence of amantadine resistance among circulating European porcine influenza A viruses.

Krumbholz A, Schmidtke M, Bergmann S, Motzke S, Bauer K, Stech J, D?rrwald R, Wutzler P, Zell R. - Friedrich Schiller University;

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 resistence 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.

PMID: 19223487 [PubMed - as supplied by publisher]
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[gsgs]

Re: J Gen Virol. High prevalence of amantadine resistance among circulating European porcine influenza A viruses.

how/when Amantadine
resistance developed in European swine which then gave M (segment 7) to mexflu

full text here.
http://vir.sgmjournals.org/cgi/content/full/90/4/900

about how/when Amantadine
resistance developed in European swine which then
gave M (segment 7) to ****** = novel H1N1(2009)


> As there are no indications that pigs ever have been treated with
> amantadine in Europe, the emergence of amantadine resistance
> has very likely a natural cause.



The reason for the astounding spread of resistant porcine virus strains remains elusive,
but may not be unusual. In recent years, the prevalence of adamantane-resistant human
influenza viruses has been increasing rapidly (compare Bright et al., 2005; Deyde et al., 2007).
Previous investigations indicate that two mechanisms may account for the amantadine
resistance of human FLUAVs: spontaneous substitutions occurring with low incidence
(Ziegler et al., 1999), and the selection of resistant variants upon antiviral therapy
(Shiraishi et al., 2003). Interestingly, excessive use of adamantane inhibitors may
not explain upsurge of resistant human strains in many countries. Simonsen et al. (2007),
observed that a 4+4 segment reassortment event favoured resistant strains due to
fitness-enhancing mutations at other genomic sites. For swFLUAVs, the sequence
data do not allow the demonstration of such a hitchhiking effect (data not shown).
Also, selection of resistant strains upon antiviral therapy appears to be an unlikely
mechanism, but a bottleneck effect might be a reasonable explanation
(Domingo & Holland, 1997).