Article: The 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses

File Download

re01.htm

Links for fulltext
(May Require Subscription)

Publisher Website: 10.1016/j.antiviral.2011.11.006
Scopus: eid_2-s2.0-84355165239
PMID: 22138712

Supplementary

Citations:
- Scopus:
- Web of Science:
- PubMed Central:
Item Statistics (The Hub)
Appears in Collections:
- Microbiology: Journal/Magazine Articles

Title	The 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses
Authors	Wu, WL2 Lau, SY2 Chen, Y1 Wang, G3 Mok, BWY2 Wen, X2 Wang, P2 Song, W2 Lin, T1 Chan, KH2 Yuen, KY2 Chen, HL2 3
Keywords	H1N1 Influenza Neuraminidase Oseltamivir Resistance H275Y
Issue Date	2012
Publisher	Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
Citation	Antiviral Research, 2012, v. 93 n. 1, p. 144-153 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.antiviral.2011.11.006
Abstract	A naturally-occurring H275Y oseltamivir resistant variant of influenza A (H1N1) virus emerged in 2007, subsequently becoming prevalent worldwide, via an undetermined mechanism. To understand the antigenic properties of the H275Y variant, oseltamivir resistant and susceptible strains of H1N1 viruses were analyzed by hemagglutination inhibition (HI) and microneutralization assays. HI analysis with H1-positive sera obtained from seasonal flu vaccine immunized and non-immunized individuals, and H1-specific monoclonal antibodies, revealed that resistant strains exhibited a reduced reactivity to these antisera and antibodies in the HI assay, as compared to susceptible strains. Neutralization assay testing demonstrated that oseltamivir resistant H1N1 strains are also less susceptible to antibody inhibition during infection. Mice inoculated with a resistant clinical isolate exhibit 4-fold lower virus-specific antibody titers than mice infected with a susceptible strain under the same conditions. Resistant and sensitive variants of 2009 pandemic H1N1 virus did not exhibit such differences. While HA1 and NA phylogenetic trees show that both oseltamivir resistant and susceptible strains belong to clade 2B, NA D354G and HA A189T substitutions were found exclusively, and universally, in oseltamivir resistant variants. Our results suggest that the reduced susceptibility to antibody inhibition and lesser in vivo immunogenicity of the oseltamivir resistant 2008-2009 H1N1 influenza A virus is conferred by coupled NA and HA mutations, and may contribute to the prevalence of this H1N1 variant. © 2011 Elsevier B.V.
ISSN	0166-3542 2011 Impact Factor: 4.301 2011 SCImago Journal Rankings: 0.393
DOI	http://dx.doi.org/10.1016/j.antiviral.2011.11.006
ISI Accession Number ID	WOS:000300802100018
PubMed Central ID	PMC3243069
References	References in Scopus

DC Field	Value
dc.contributor.author	Wu, WL
dc.contributor.author	Lau, SY
dc.contributor.author	Chen, Y
dc.contributor.author	Wang, G
dc.contributor.author	Mok, BWY
dc.contributor.author	Wen, X
dc.contributor.author	Wang, P
dc.contributor.author	Song, W
dc.contributor.author	Lin, T
dc.contributor.author	Chan, KH
dc.contributor.author	Yuen, KY
dc.contributor.author	Chen, HL
dc.date.accessioned	2012-08-08T08:52:03Z
dc.date.available	2012-08-08T08:52:03Z
dc.date.issued	2012
dc.description.abstract	A naturally-occurring H275Y oseltamivir resistant variant of influenza A (H1N1) virus emerged in 2007, subsequently becoming prevalent worldwide, via an undetermined mechanism. To understand the antigenic properties of the H275Y variant, oseltamivir resistant and susceptible strains of H1N1 viruses were analyzed by hemagglutination inhibition (HI) and microneutralization assays. HI analysis with H1-positive sera obtained from seasonal flu vaccine immunized and non-immunized individuals, and H1-specific monoclonal antibodies, revealed that resistant strains exhibited a reduced reactivity to these antisera and antibodies in the HI assay, as compared to susceptible strains. Neutralization assay testing demonstrated that oseltamivir resistant H1N1 strains are also less susceptible to antibody inhibition during infection. Mice inoculated with a resistant clinical isolate exhibit 4-fold lower virus-specific antibody titers than mice infected with a susceptible strain under the same conditions. Resistant and sensitive variants of 2009 pandemic H1N1 virus did not exhibit such differences. While HA1 and NA phylogenetic trees show that both oseltamivir resistant and susceptible strains belong to clade 2B, NA D354G and HA A189T substitutions were found exclusively, and universally, in oseltamivir resistant variants. Our results suggest that the reduced susceptibility to antibody inhibition and lesser in vivo immunogenicity of the oseltamivir resistant 2008-2009 H1N1 influenza A virus is conferred by coupled NA and HA mutations, and may contribute to the prevalence of this H1N1 variant. © 2011 Elsevier B.V.
dc.description.nature	link_to_OA_fulltext
dc.identifier.citation	Antiviral Research, 2012, v. 93 n. 1, p. 144-153 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.antiviral.2011.11.006
dc.identifier.citeulike	10090132
dc.identifier.doi	http://dx.doi.org/10.1016/j.antiviral.2011.11.006
dc.identifier.epage	153
dc.identifier.hkuros	208499
dc.identifier.isi	WOS:000300802100018
dc.identifier.issn	0166-3542 2011 Impact Factor: 4.301 2011 SCImago Journal Rankings: 0.393
dc.identifier.issue	1
dc.identifier.pmcid	PMC3243069
dc.identifier.pmid	22138712
dc.identifier.scopus	eid_2-s2.0-84355165239
dc.identifier.spage	144
dc.identifier.uri	http://hdl.handle.net/10722/157664
dc.identifier.volume	93
dc.language	eng
dc.publisher	Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
dc.publisher.place	Netherlands
dc.relation.ispartof	Antiviral Research
dc.relation.references	References in Scopus
dc.subject.mesh	Young Adult
dc.subject.mesh	Viral proteins - genetics - immunology - metabolism
dc.subject.mesh	Phylogeny
dc.subject.mesh	Oseltamivir - pharmacology
dc.subject.mesh	Orthomyxoviridae infections - immunology
dc.subject.mesh	Neuraminidase - genetics - immunology - metabolism
dc.subject.mesh	Mutation
dc.subject.mesh	Middle aged
dc.subject.mesh	Mice, Inbred BALB/c
dc.subject.mesh	Mice
dc.subject.mesh	Influenza A virus, H1N1 subtype - drug effects - genetics - immunology
dc.subject.mesh	Humans
dc.subject.mesh	Genotype
dc.subject.mesh	Female
dc.subject.mesh	Drug resistance, Viral - genetics
dc.subject.mesh	Cell line
dc.subject.mesh	Antiviral agents - pharmacology
dc.subject.mesh	Antibodies, Monoclonal - immunology
dc.subject.mesh	Animals
dc.subject.mesh	Amino acid substitution
dc.subject.mesh	Adult
dc.subject	H1N1
dc.subject	Influenza
dc.subject	Neuraminidase
dc.subject	Oseltamivir
dc.subject	Resistance
dc.subject	H275Y
dc.title	The 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses
dc.type	Article

<?xml encoding="utf-8" version="1.0"?><item><contributor.author>Wu, WL</contributor.author><contributor.author>Lau, SY</contributor.author><contributor.author>Chen, Y</contributor.author><contributor.author>Wang, G</contributor.author><contributor.author>Mok, BWY</contributor.author><contributor.author>Wen, X</contributor.author><contributor.author>Wang, P</contributor.author><contributor.author>Song, W</contributor.author><contributor.author>Lin, T</contributor.author><contributor.author>Chan, KH</contributor.author><contributor.author>Yuen, KY</contributor.author><contributor.author>Chen, HL</contributor.author><date.accessioned>2012-08-08T08:52:03Z</date.accessioned><date.available>2012-08-08T08:52:03Z</date.available><date.issued>2012</date.issued><identifier.citation>Antiviral Research, 2012, v. 93 n. 1, p. 144-153</identifier.citation><identifier.issn>0166-3542</identifier.issn><identifier.uri>http://hdl.handle.net/10722/157664</identifier.uri><description.abstract>A naturally-occurring H275Y oseltamivir resistant variant of influenza A (H1N1) virus emerged in 2007, subsequently becoming prevalent worldwide, via an undetermined mechanism. To understand the antigenic properties of the H275Y variant, oseltamivir resistant and susceptible strains of H1N1 viruses were analyzed by hemagglutination inhibition (HI) and microneutralization assays. HI analysis with H1-positive sera obtained from seasonal flu vaccine immunized and non-immunized individuals, and H1-specific monoclonal antibodies, revealed that resistant strains exhibited a reduced reactivity to these antisera and antibodies in the HI assay, as compared to susceptible strains. Neutralization assay testing demonstrated that oseltamivir resistant H1N1 strains are also less susceptible to antibody inhibition during infection. Mice inoculated with a resistant clinical isolate exhibit 4-fold lower virus-specific antibody titers than mice infected with a susceptible strain under the same conditions. Resistant and sensitive variants of 2009 pandemic H1N1 virus did not exhibit such differences. While HA1 and NA phylogenetic trees show that both oseltamivir resistant and susceptible strains belong to clade 2B, NA D354G and HA A189T substitutions were found exclusively, and universally, in oseltamivir resistant variants. Our results suggest that the reduced susceptibility to antibody inhibition and lesser in vivo immunogenicity of the oseltamivir resistant 2008-2009 H1N1 influenza A virus is conferred by coupled NA and HA mutations, and may contribute to the prevalence of this H1N1 variant. &#169; 2011 Elsevier B.V.</description.abstract><language>eng</language><publisher>Elsevier BV. The Journal&apos;s web site is located at http://www.elsevier.com/locate/antiviral</publisher><relation.ispartof>Antiviral Research</relation.ispartof><subject>H1N1</subject><subject>Influenza</subject><subject>Neuraminidase</subject><subject>Oseltamivir</subject><subject>Resistance</subject><subject>H275Y</subject><subject.mesh>Young Adult</subject.mesh><subject.mesh>Viral proteins - genetics - immunology - metabolism</subject.mesh><subject.mesh>Phylogeny</subject.mesh><subject.mesh>Oseltamivir - pharmacology</subject.mesh><subject.mesh>Orthomyxoviridae infections - immunology</subject.mesh><subject.mesh>Neuraminidase - genetics - immunology - metabolism</subject.mesh><subject.mesh>Mutation</subject.mesh><subject.mesh>Middle aged</subject.mesh><subject.mesh>Mice, Inbred BALB/c</subject.mesh><subject.mesh>Mice</subject.mesh><subject.mesh>Influenza A virus, H1N1 subtype - drug effects - genetics - immunology</subject.mesh><subject.mesh>Humans</subject.mesh><subject.mesh>Genotype</subject.mesh><subject.mesh>Female</subject.mesh><subject.mesh>Drug resistance, Viral - genetics</subject.mesh><subject.mesh>Cell line</subject.mesh><subject.mesh>Antiviral agents - pharmacology</subject.mesh><subject.mesh>Antibodies, Monoclonal - immunology</subject.mesh><subject.mesh>Animals</subject.mesh><subject.mesh>Amino acid substitution</subject.mesh><subject.mesh>Adult</subject.mesh><title>The 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses</title><type>Article</type><description.nature>link_to_OA_fulltext</description.nature><identifier.doi>10.1016/j.antiviral.2011.11.006</identifier.doi><identifier.pmid>22138712</identifier.pmid><identifier.pmcid>PMC3243069</identifier.pmcid><identifier.scopus>eid_2-s2.0-84355165239</identifier.scopus><identifier.hkuros>208499</identifier.hkuros><relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-84355165239&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references><identifier.volume>93</identifier.volume><identifier.issue>1</identifier.issue><identifier.spage>144</identifier.spage><identifier.epage>153</identifier.epage><identifier.isi>WOS:000300802100018</identifier.isi><publisher.place>Netherlands</publisher.place><identifier.citeulike>10090132</identifier.citeulike><bitstream.url>http://hub.hku.hk/bitstream/10722/157664/1/re01.htm</bitstream.url></item>

Author Affiliations

Xiamen University
The University of Hong Kong
Shantou University