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

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.

Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A H5N1 viruses in ferrets

“…Infection with HPAI A(H5N1) viruses bearing potential genetic indicators of pathogenicity can cause mild to severe disease in mammalian models (Herfst et al, 2012; Imai et al, 2012; Maines et al, 2005; Suguitan et al, 2012; Thor et al, 2015). To evaluate the relative virulence of selected clade 2 A(H5N1) viruses, ferrets were inoculated i.n.…”

“…Established surveillance and analysis of currently circulating viruses in poultry have continually tracked and identified genetically and antigenically distinct A(H5N1) lineages (Creanga et al, 2013; Gerloff et al, 2014; Thor et al, 2015). While genetic analysis of the hemagglutinin (HA) gene of these lineages has resulted in the classification of isolates into multiple clades and subclades, only viruses from clades 0, 1, 2, and 7 have crossed the species barrier to cause disease and death in humans (Abdel-Ghafar et al, 2008).…”

Highly Pathogenic Avian Influenza Virus A/H5N1 Infection in Vaccinated Meat Duck Flocks in the Mekong Delta of Vietnam

“…Since 2012, when clade 2.3.2.1c was first identified in Vietnam, only one (fatal) human case has been confirmed as infected with this clade (in January 2014) in the Mekong Delta province of Dong Thap, adjacent to Tien Giang province, where this study was conducted (WHO, ; Thor et al., ). In Vietnam, a total of 127 HPAI H5N1 human cases have been confirmed from 2003 to 2014 (WHO, ), and for 87 human cases, clade information is available.…”

“…Since 2011, clade 2.3.2.1 has been replacing the previously dominating clade 2.3.4 in northern and central Vietnam. This clade subsequently evolved into its variants (2.3.2.1a/b/c), and became widespread throughout the Since 2012, when clade 2.3.2.1c was first identified in Vietnam, only one (fatal) human case has been confirmed as infected with this clade (in January 2014) in the Mekong Delta province of Dong Thap, adjacent to Tien Giang province, where this study was conducted (WHO, 2014;Thor et al, 2015). In Vietnam, a total of 127 HPAI H5N1 human cases have been confirmed from 2003(WHO, 2015, and for 87 human cases, clade information is available.…”

Chiral MoS2 Quantum Dots: Dual‐Mode Detection Approaches for Avian Influenza Viruses

“…We have chosen influenza virus detection as a model analyte because of its high pathogenicity in the poultry industry as well as the associated concerns to humans due to its transmission ability from infected domestic poultry to humans and then from person‐to‐person. The high mortality rate of the avian influenza virus in both poultry and humans could have a significant effect on the global economy, with a particularly strong impact on social health care . Therefore, a rapid and sensitive bioassay for influenza virus detection could be particularly useful for the timely response to overcome future pandemic threats.…”