Limits...
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 PB2 gene.Neighbor-joining phylogenetic tree of the PB2 gene of VN3 (clade 1-like, Fig 2a) and VN12 (clade 2.3.2.1a-like, Fig 2b) highly pathogenic avian influenza A (H5N1) virus. Red virus strain names denote a WHO candidate reassortant vaccine virus. 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. The phylogenetic groupings for this gene are representative of all internal genes. Phylogenetic analysis of other internal genes can be found in S1–S10 Figs).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526568&req=5

pone.0133867.g002: Neighbor-joining phylogenetic analysis of the PB2 gene.Neighbor-joining phylogenetic tree of the PB2 gene of VN3 (clade 1-like, Fig 2a) and VN12 (clade 2.3.2.1a-like, Fig 2b) highly pathogenic avian influenza A (H5N1) virus. Red virus strain names denote a WHO candidate reassortant vaccine virus. 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. The phylogenetic groupings for this gene are representative of all internal genes. Phylogenetic analysis of other internal genes can be found in S1–S10 Figs).

Mentions: Internal gene analysis of A/Vietnam/VP12-3/2012 and A/Vietnam/CD12-76/2012 classified these viruses as genotype VN3 as defined by Wan et al. [10]. Phylogenetic analysis grouped each gene segment with other viruses of this genotype (Fig 2a), and BLAST analysis of the GISAID database (http://platform.gisaid.org/epi3/frontend#20414d) showed each gene segment to have ≥ 99.3% ID with viruses having gene constellations consistent with VN3 [10,12,13](data not shown). The analysis of internal genes from 2013 isolates revealed evidence of a reassortment event between H5N1 viruses of genotype VN3 and VN12. Each of the internal genes from A/Vietnam/VP13-28H/2013 and A/Vietnam/VP39/2013 were closely related to genes found in 2.3.2.1a lineage (Hubei-like) viruses with high nucleotide identity to other viruses of genotype VN12 (≥99.2%). This gene arrangement differed from the isolates obtained in 2012 where all gene segments were related to ancestral clade 1 viruses (Fig 2b).


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 PB2 gene.Neighbor-joining phylogenetic tree of the PB2 gene of VN3 (clade 1-like, Fig 2a) and VN12 (clade 2.3.2.1a-like, Fig 2b) highly pathogenic avian influenza A (H5N1) virus. Red virus strain names denote a WHO candidate reassortant vaccine virus. 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. The phylogenetic groupings for this gene are representative of all internal genes. Phylogenetic analysis of other internal genes can be found in S1–S10 Figs).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133867.g002: Neighbor-joining phylogenetic analysis of the PB2 gene.Neighbor-joining phylogenetic tree of the PB2 gene of VN3 (clade 1-like, Fig 2a) and VN12 (clade 2.3.2.1a-like, Fig 2b) highly pathogenic avian influenza A (H5N1) virus. Red virus strain names denote a WHO candidate reassortant vaccine virus. 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. The phylogenetic groupings for this gene are representative of all internal genes. Phylogenetic analysis of other internal genes can be found in S1–S10 Figs).
Mentions: Internal gene analysis of A/Vietnam/VP12-3/2012 and A/Vietnam/CD12-76/2012 classified these viruses as genotype VN3 as defined by Wan et al. [10]. Phylogenetic analysis grouped each gene segment with other viruses of this genotype (Fig 2a), and BLAST analysis of the GISAID database (http://platform.gisaid.org/epi3/frontend#20414d) showed each gene segment to have ≥ 99.3% ID with viruses having gene constellations consistent with VN3 [10,12,13](data not shown). The analysis of internal genes from 2013 isolates revealed evidence of a reassortment event between H5N1 viruses of genotype VN3 and VN12. Each of the internal genes from A/Vietnam/VP13-28H/2013 and A/Vietnam/VP39/2013 were closely related to genes found in 2.3.2.1a lineage (Hubei-like) viruses with high nucleotide identity to other viruses of genotype VN12 (≥99.2%). This gene arrangement differed from the isolates obtained in 2012 where all gene segments were related to ancestral clade 1 viruses (Fig 2b).

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