Rhiza Labs FluTracker Forum

Antivir Ther. 2010;15(5):721-6.

Novel influenza A(H1N1) 2009 in vitro reassortant viruses with oseltamivir resistance.
Ottmann M, Duchamp MB, Casalegno JS, Frobert E, Moulès V, Ferraris O, Valette M, Escuret V, Lina B.

Université de Lyon, France. michele.ottmann@univ-lyon1.fr

Abstract
BACKGROUND: With the recent emergence of the novel A(H1N1) virus in 2009, the efficacy of available drugs, such as neuraminidase (NA) inhibitors, is of great concern for good patient care. Influenza viruses are known to be able to acquire resistance. In 2007, A(H1N1) viruses related to A/Brisbane/59/2007 (H1N1) (A[H1N1] Brisbane-like virus), which are naturally resistant to oseltamivir, emerged. Resistance to oseltamivir can be acquired either by spontaneous mutation in the NA (H275Y in N1), or by reassortment with a mutated NA. It is therefore crucial to determine the risk of pandemic A(H1N1) 2009 virus acquiring resistance against oseltamivir by reassortment.

METHODS: We estimated the capacity of reassortment between the A(H1N1) 2009 virus and an oseltamivir-resistant A(H1N1) Brisbane-like virus by in vitro coinfections of influenza-permissive cells. The screening and the analysis of reassortant viruses was performed by specific reverse transcriptase PCRs and by sequencing.

RESULTS: Out of 50 analysed reassortant, two harboured the haemagglutinin (HA) segment from the pandemic A(H1N1) 2009 virus and the mutated NA originated from the A(H1N1) Brisbane-like virus. The replicating capacities of these viruses were measured, showing no difference as compared to the two parental strains, suggesting that acquisition of the mutated NA segment did not impair viral fitness in vitro.

CONCLUSIONS: Our results suggest that the novel A(H1N1) 2009 virus can acquire by in vitro genetic reassortment the H275Y mutated NA segment conferring resistance to oseltamivir.

PMID: 20710053 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/20710053

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LOCUS JF429402 1701 bp cRNA linear VRL 12-MAR-2011
DEFINITION Influenza A virus (A/Lyon/969/2009(H1N1)) segment 4 hemagglutinin
(HA) gene, complete cds.
ACCESSION JF429402
VERSION JF429402.1 GI:325451709
DBLINK Project: 37813
KEYWORDS .
SOURCE Influenza A virus (A/Lyon/969/2009(H1N1))
ORGANISM Influenza A virus (A/Lyon/969/2009(H1N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1701)
AUTHORS Ottmann,M., Duchamp,M.B., Casalegno,J.S., Frobert,E., Moules,V.,
Ferraris,O., Valette,M., Escuret,V. and Lina,B.
TITLE Novel influenza A(H1N1) 2009 in vitro reassortant viruses with
oseltamivir resistance
JOURNAL Antivir. Ther. (Lond.) 15 (5), 721-726 (2010)
PUBMED 20710053
REFERENCE 2 (bases 1 to 1701)
AUTHORS Ottmann,M., Erny,A., Traversier,A., Rivat,N., Lines,L.,
Sabatier,M., Valette,M., Escuret,V., Bouscambert-Duchamp,M.,
Caro,V., Barthelemy,M., Casalegno,J.-S., Ferraris,O., Lina,B. and
Prog-Victoir,E.
TITLE Surveillance of Influenza in France sud by Centre National de
Reference Influenza France Sud and Genotyping of Pathogens and
Public Health platform, Institut Pasteur
JOURNAL Unpublished
REFERENCE 3 (bases 1 to 1701)
AUTHORS Ottmann,M., Bouscambert-Duchamp,M., Casalegno,J.-S., Frobert,E.,
Ferraris,O., Valette,M., Escuret,V., Lina,B., Erny,A.,
Barthelemy,M., Traversier,A., Rivat,N., Lines,L., Sabatier,M.,
Caro,V., Ferraris,O. and Prog-Victoir,E.
TITLE Direct Submission
JOURNAL Submitted (18-FEB-2011) Laboratoire de Virologie, Universite Claude
Bernard - Lyon 1, rue Guillaume Paradin, Lyon 69 008, France
FEATURES Location/Qualifiers
source 1..1701
/organism="Influenza A virus (A/Lyon/969/2009(H1N1))"
/mol_type="viral cRNA"
/strain="A/Lyon/969/2009"
/serotype="H1N1"
/host="Homo sapiens"
/db_xref="taxon:990089"
/segment="4"
/country="France"
/collection_date="Jun-2009"
/note="lineage: swl"
gene 1..1701
/gene="HA"
CDS 1..1701
/gene="HA"
/codon_start=1
/product="hemagglutinin"
/protein_id="ADZ13523.1"
/db_xref="GI:325451710"
/translation="MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTVT
HSVNLLEDKHNGKLCKLRGVAPLHLGKCNIAGWILGNPECESLSTASSWSYIVETSSS
DNGTCYPGDFIDYEELREQLSSVSSFERFEIFPKTSSWPNHDSNKGVTAACPHAGAKS
FYKNLIWLVKKGNSYPKLSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADAYVFV
GSSRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVVPRYAFAMER
NAGSGIIISDTPVHDCNTTCQTPKGAINTSLPFQNIHPITIGKCPKYVKSTKLRLATG
LRNVPSIQSRGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGSGYAADLKSTQNAIDEI
TNKVNSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAELLVLLENER
TLDYHDSNVKNLYEKVRSQLKNNAKEIGNGCFEFYHKCDNTCMESVKNGTYDYPKYSE
EAKLNREEIDGVKLESTRIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI
"
ORIGIN
1 atgaaggcaa tactagtagt tctgctatat acatttgcaa ccgcaaatgc agacacatta
61 tgtataggtt atcatgcgaa caattcaaca gacactgtag acacagtact agaaaagaat
121 gtaacagtaa cacactctgt taaccttcta gaagacaagc ataacgggaa actatgcaaa
181 ctaagagggg tagccccatt gcatttgggt aaatgtaaca ttgctggctg gatcctggga
241 aatccagagt gtgaatcact ctccacagca agctcatggt cctacattgt ggaaacatct
301 agttcagaca atggaacgtg ttacccagga gatttcatcg attatgagga gctaagagag
361 caattgagct cagtgtcatc atttgaaagg tttgagatat tccccaagac aagttcatgg
421 cccaatcatg actcgaacaa aggtgtaacg gcagcatgtc ctcatgctgg agcaaaaagc
481 ttctacaaaa atttaatatg gctagttaaa aaaggaaatt catacccaaa gctcagcaaa
541 tcctacatta atgataaagg gaaagaagtc ctcgtgctat ggggcattca ccatccatct
601 actagtgctg accaacaaag tctctatcag aatgcagatg catatgtttt tgtggggtca
661 tcaagataca gcaagaagtt caagccggaa atagcaataa gacccaaagt gagggatcaa
721 gaagggagaa tgaactatta ctggacacta gtagagccgg gagacaaaat aacattcgaa
781 gcaactggaa atctagtggt accgagatat gcattcgcaa tggaaagaaa tgctggatct
841 ggtattatca tttcagatac accagtccac gattgcaata caacttgtca gacacccaag
901 ggtgctataa acaccagcct cccatttcag aatatacatc cgatcacaat tggaaaatgt
961 ccaaaatatg taaaaagcac aaaattgaga ctggccacag gattgaggaa tgtcccgtct
1021 attcaatcta gaggcctatt tggggccatt gccggtttca ttgaaggggg gtggacaggg
1081 atggtagatg gatggtacgg ttatcaccat caaaatgagc aggggtcagg atatgcagcc
1141 gacctgaaga gcacacagaa tgccattgac gagattacta acaaagtaaa ttctgttatt
1201 gaaaagatga atacacagtt cacagcagta ggtaaagagt tcaaccacct ggaaaaaaga
1261 atagagaatt taaataaaaa agttgatgat ggtttcctgg acatttggac ttacaatgcc
1321 gaactgttgg ttctattgga aaatgaaaga actttggact accacgattc aaatgtgaag
1381 aacttatatg aaaaggtaag aagccagcta aaaaacaatg ccaaggaaat tggaaacggc
1441 tgctttgaat tttaccacaa atgcgataac acgtgcatgg aaagtgtcaa aaatgggact
1501 tatgactacc caaaatactc agaggaagca aaattaaaca gagaagaaat agatggggta
1561 aagctggaat caacaaggat ttaccagatt ttggcgatct attcaactgt cgccagttca
1621 ttggtactgg tagtctccct gggggcaatc agtttctgga tgtgctctaa tgggtctcta
1681 cagtgtagaa tatgtattta a

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