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Detection and Characterization of Clade 1 Reassortant H5N1 Viruses Isolated from Human Cases in Vietnam during 2013.

Thor SW, Nguyen H, Balish A, Hoang AN, Gustin KM, Nhung PT, Jones J, Thu NN, Davis W, Ngoc TN, Jang Y, Sleeman K, Villanueva J, Kile J, Gubareva LV, Lindstrom S, Tumpey TM, Davis CT, Long NT - PLoS ONE (2015)

Bottom Line: Highly pathogenic avian influenza (HPAI) H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003.Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012) with comparable hemagglutination inhibition titers as the homologous antigen.Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses.

View Article: PubMed Central - PubMed

Affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

ABSTRACT
Highly pathogenic avian influenza (HPAI) H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003. Human infections with HPAI H5N1 are of concern due to a high mortality rate and the potential for the emergence of pandemic viruses with sustained human-to-human transmission. Viruses isolated from humans in southern Vietnam have been classified as clade 1 with a single genome constellation (VN3) since their earliest detection in 2003. This is consistent with detection of this clade/genotype in poultry viruses endemic to the Mekong River Delta and surrounding regions. Comparison of H5N1 viruses detected in humans from southern Vietnamese provinces during 2012 and 2013 revealed the emergence of a 2013 reassortant virus with clade 1.1.2 hemagglutinin (HA) and neuraminidase (NA) surface protein genes but internal genes derived from clade 2.3.2.1a viruses (A/Hubei/1/2010-like; VN12). Closer analysis revealed mutations in multiple genes of this novel genotype (referred to as VN49) previously associated with increased virulence in animal models and other markers of adaptation to mammalian hosts. Despite the changes identified between the 2012 and 2013 genotypes analyzed, their virulence in a ferret model was similar. Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012) with comparable hemagglutination inhibition titers as the homologous antigen. Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses.

No MeSH data available.


Related in: MedlinePlus

Neighbor-joining phylogenetic analysis of the HA and NA gene.Neighbor-joining phylogenetic tree of the HA (Fig 1a) and NA (Fig 1b) genes of clade 1 highly pathogenic avian influenza A (H5N1) viruses. Red virus strain names denote a WHO candidate reassortant vaccine virus for clade 1. Red branching denotes human cases. The 2012/2013 human cases of H5N1 from Vietnam are denoted by a green strain name. Viruses previously classified with a specific Vietnam genotype are labeled parenthetically with the genotype at the end of the strain name (e.g. VN3, VN12). Bootstraps greater than 70 generated from 1,000 replicates are shown at branch nodes. The scale bar represents nucleotide substitutions per site.
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pone.0133867.g001: Neighbor-joining phylogenetic analysis of the HA and NA gene.Neighbor-joining phylogenetic tree of the HA (Fig 1a) and NA (Fig 1b) genes of clade 1 highly pathogenic avian influenza A (H5N1) viruses. Red virus strain names denote a WHO candidate reassortant vaccine virus for clade 1. Red branching denotes human cases. The 2012/2013 human cases of H5N1 from Vietnam are denoted by a green strain name. Viruses previously classified with a specific Vietnam genotype are labeled parenthetically with the genotype at the end of the strain name (e.g. VN3, VN12). Bootstraps greater than 70 generated from 1,000 replicates are shown at branch nodes. The scale bar represents nucleotide substitutions per site.

Mentions: Phylogenetic analysis of the H5 hemagglutinin (HA) was conducted to determine the HA clades of the 2012–2013 viruses isolated from humans in Southern Vietnam. All viruses were found to share a common ancestor with A/goose/Guangdong/1/1996 and belong to either clade 1.1.1 or 1.1.2. The HA genes from the 2012 and 2013 viruses clustered spatially and temporally with related viruses; however A/Vietnam/VP13-28H/2013 and A/Vietnam/VP39/2013 both clustered closely with contemporary viruses on a separate branch (bootstrap value of 71) (Fig 1a). The HA genes from both the 2012 and 2013 viruses were similar to related Vietnamese and Cambodian viruses from either clade 1.1.1 or 1.1.2, as determined by BLAST analysis of the GISAID database (http://platform.gisaid.org/epi3/frontend#20414d) at ≥ 99.3 percent nucleotide identity (% ID) (data not shown). Only one lineage of N1 NA was found in the human viruses isolated during both 2012 and 2013. The clustering of all virus NA genes closely resembled that of the HA phylogeny; with A/Vietnam/VP12-3/2012 and A/Vietnam/CD12-76/2012 clustering with other viruses isolated in Cambodia and Vietnam during 2012 and A/Vietnam/VP13-28H/2013 and A/Vietnam/VP39/2013 grouped with other viruses isolated in 2013 on a separate branch (bootstrap value of 76) (Fig 1b). Using BLAST analysis of the GISAID database (http://platform.gisaid.org/epi3/frontend#20414d), we found all viruses to be highly similar to viruses that cluster with viruses previously identified as from the VN3 genotype at ≥ 99.3% ID (data not shown).


Detection and Characterization of Clade 1 Reassortant H5N1 Viruses Isolated from Human Cases in Vietnam during 2013.

Thor SW, Nguyen H, Balish A, Hoang AN, Gustin KM, Nhung PT, Jones J, Thu NN, Davis W, Ngoc TN, Jang Y, Sleeman K, Villanueva J, Kile J, Gubareva LV, Lindstrom S, Tumpey TM, Davis CT, Long NT - PLoS ONE (2015)

Neighbor-joining phylogenetic analysis of the HA and NA gene.Neighbor-joining phylogenetic tree of the HA (Fig 1a) and NA (Fig 1b) genes of clade 1 highly pathogenic avian influenza A (H5N1) viruses. Red virus strain names denote a WHO candidate reassortant vaccine virus for clade 1. Red branching denotes human cases. The 2012/2013 human cases of H5N1 from Vietnam are denoted by a green strain name. Viruses previously classified with a specific Vietnam genotype are labeled parenthetically with the genotype at the end of the strain name (e.g. VN3, VN12). Bootstraps greater than 70 generated from 1,000 replicates are shown at branch nodes. The scale bar represents nucleotide substitutions per site.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4526568&req=5

pone.0133867.g001: Neighbor-joining phylogenetic analysis of the HA and NA gene.Neighbor-joining phylogenetic tree of the HA (Fig 1a) and NA (Fig 1b) genes of clade 1 highly pathogenic avian influenza A (H5N1) viruses. Red virus strain names denote a WHO candidate reassortant vaccine virus for clade 1. Red branching denotes human cases. The 2012/2013 human cases of H5N1 from Vietnam are denoted by a green strain name. Viruses previously classified with a specific Vietnam genotype are labeled parenthetically with the genotype at the end of the strain name (e.g. VN3, VN12). Bootstraps greater than 70 generated from 1,000 replicates are shown at branch nodes. The scale bar represents nucleotide substitutions per site.
Mentions: Phylogenetic analysis of the H5 hemagglutinin (HA) was conducted to determine the HA clades of the 2012–2013 viruses isolated from humans in Southern Vietnam. All viruses were found to share a common ancestor with A/goose/Guangdong/1/1996 and belong to either clade 1.1.1 or 1.1.2. The HA genes from the 2012 and 2013 viruses clustered spatially and temporally with related viruses; however A/Vietnam/VP13-28H/2013 and A/Vietnam/VP39/2013 both clustered closely with contemporary viruses on a separate branch (bootstrap value of 71) (Fig 1a). The HA genes from both the 2012 and 2013 viruses were similar to related Vietnamese and Cambodian viruses from either clade 1.1.1 or 1.1.2, as determined by BLAST analysis of the GISAID database (http://platform.gisaid.org/epi3/frontend#20414d) at ≥ 99.3 percent nucleotide identity (% ID) (data not shown). Only one lineage of N1 NA was found in the human viruses isolated during both 2012 and 2013. The clustering of all virus NA genes closely resembled that of the HA phylogeny; with A/Vietnam/VP12-3/2012 and A/Vietnam/CD12-76/2012 clustering with other viruses isolated in Cambodia and Vietnam during 2012 and A/Vietnam/VP13-28H/2013 and A/Vietnam/VP39/2013 grouped with other viruses isolated in 2013 on a separate branch (bootstrap value of 76) (Fig 1b). Using BLAST analysis of the GISAID database (http://platform.gisaid.org/epi3/frontend#20414d), we found all viruses to be highly similar to viruses that cluster with viruses previously identified as from the VN3 genotype at ≥ 99.3% ID (data not shown).

Bottom Line: Highly pathogenic avian influenza (HPAI) H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003.Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012) with comparable hemagglutination inhibition titers as the homologous antigen.Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses.

View Article: PubMed Central - PubMed

Affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

ABSTRACT
Highly pathogenic avian influenza (HPAI) H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003. Human infections with HPAI H5N1 are of concern due to a high mortality rate and the potential for the emergence of pandemic viruses with sustained human-to-human transmission. Viruses isolated from humans in southern Vietnam have been classified as clade 1 with a single genome constellation (VN3) since their earliest detection in 2003. This is consistent with detection of this clade/genotype in poultry viruses endemic to the Mekong River Delta and surrounding regions. Comparison of H5N1 viruses detected in humans from southern Vietnamese provinces during 2012 and 2013 revealed the emergence of a 2013 reassortant virus with clade 1.1.2 hemagglutinin (HA) and neuraminidase (NA) surface protein genes but internal genes derived from clade 2.3.2.1a viruses (A/Hubei/1/2010-like; VN12). Closer analysis revealed mutations in multiple genes of this novel genotype (referred to as VN49) previously associated with increased virulence in animal models and other markers of adaptation to mammalian hosts. Despite the changes identified between the 2012 and 2013 genotypes analyzed, their virulence in a ferret model was similar. Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012) with comparable hemagglutination inhibition titers as the homologous antigen. Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses.

No MeSH data available.


Related in: MedlinePlus