Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic Republic

Boltz, David A.; Douangngeun, Bounlom; Phommachanh, Phouvong; Sinthasak, Settha; Mondry, Ricarda; Obert, Caroline; Seiler, Patrick; Keating, Rachael; Suzuki, Yasuo; Hiramatsu, Hiroaki; Govorkova, Elena A.; Webster, Robert G.

doi:10.1099/vir.0.017459-0

Cited by 93 publications

(88 citation statements)

References 43 publications

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“…Our phylogenetic analysis showed that the PB1 gene segment of the isolate had the highest evolutionary relationship with that of the A/Chicken/ Laos/P0130/07 (H5N1) virus, which was highly pathogenic in chickens and mice (2). Our molecular analysis revealed that the PA protein of the isolate possessed one of the known pathogenic markers examined herein: an isoleucine residue at position 97 that has been associated with enhanced virulence and replication in mice (24).…”

Section: Discussionmentioning

confidence: 85%

Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation

Nam

Kim

Song

et al. 2011

J Virol

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The migratory waterfowl of the world are considered to be the natural reservoir of influenza A viruses. Of the 16 hemagglutinin subtypes of avian influenza viruses, the H6 subtype is commonly perpetuated in its natural hosts and is of concern due to its potential to be a precursor of highly pathogenic influenza viruses by reassortment. During routine influenza surveillance, we isolated an unconventional H6N5 subtype of avian influenza virus. Experimental infection of mice revealed that this isolate replicated efficiently in the lungs, subsequently spread systemically, and caused lethality. The isolate also productively infected ferrets, with direct evidence of contact transmission, but no disease or transmission was seen in pigs. Although the isolate possessed the conserved receptor-binding site sequences of avian influenza viruses, it exhibited relatively low replication efficiencies in ducks and chickens. Our genetic and molecular analyses of the isolate revealed that its PB1 sequence showed the highest evolutionary relationship to those of highly pathogenic H5N1 avian influenza viruses and that its PA protein had an isoleucine residue at position 97 (a representative virulence marker). Further studies will be required to examine why our isolate has the virologic characteristics of mammalian influenza viruses but the archetypal receptor binding profiles of avian influenza viruses, as well as to determine whether its potential virulence markers (PB1 analogous to those of H5N1 viruses or isoleucine residue at position 97 within PA) could render it highly pathogenic in mice.

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Section: Discussionmentioning

confidence: 85%

Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation

Nam

Kim

Song

et al. 2011

J Virol

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“…2009; Smith et al, 2009). It was further isolated in Russia, South Korea, Japan and Laos in 2008 (Boltz et al, 2010;J. Chen et al, 2009;Kim et al, 2010;Nguyen et al, 2009;Uchida et al, 2008) (Kou et al, 2009;Smith et al, 2009;Uchida et al, 2008), may play an important role in the circulation of the viruses in poultry in this region, because many domestic fowls (especially ducks) share the same niches as wild birds, although it cannot be excluded that wild bird populations are continuously infected by poultry sources.…”

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confidence: 99%

Molecular epidemiological surveys of H5 subtype highly pathogenic avian influenza viruses in poultry in China during 2007-2009

Jiang

Liu

Chen

et al. 2010

Journal of General Virology

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“…Among them, clade 2 showed significant genetic variation into numerous subclades [7]. In addition, genetic reassortment has resulted in rapid viral evolution and created favorable circumstances for the emergence of new genotypes that may possess unique characteristics [8][9][10][11]. Thus, it is imperative to continue characterizing newly isolated HPAIVs to monitor for genetic changes that alter the viral phenotype.…”

Section: Introductionmentioning

confidence: 99%

Genetic characterization of an H5N1 avian influenza virus from a vaccinated duck flock in Vietnam

Bui

Ogawa²,

Trinh³

et al. 2014

Virus Genes

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This study reports the genetic characterization of a highly pathogenic avian influenza virus subtype H5N1 isolated from a moribund domestic duck in central Vietnam during 2012. In the moribund duck's flock, within 6 days after vaccination with a commercial H5N1 vaccine (Re-5) to 59-day-old birds, 120 out of 2,000 ducks died. Genetic analysis revealed a substantial number of mutations in the HA gene of the isolate in comparison with the vaccine strains, Re-1 and Re-5. Similar mutations were also found in selected Vietnamese H5N1 strains isolated since 2009. Mutations in the HA gene involved positions at antigenic sites associated with antibody binding and also neutralizing epitopes, with some of the mutations resulting in the modification of N-linked glycosylation of the HA. Those mutations may be related to the escape of virus from antibody binding and the infection of poultry, interpretations which may be confirmed through a reverse genetics approach. The virus also carried an amino acid substitution in the M2, which conferred a reduced susceptibility to amantadine, but no neuraminidase inhibitor resistance markers were found in the viral NA gene. Additional information including vaccination history in the farm and the surrounding area is needed to fully understand the background of this outbreak. Such understanding and expanded monitoring of the H5N1 influenza viruses circulating in Vietnam is an urgent need to provide updated information to improve effective vaccine strain selection and vaccination protocols, aiding disease control, and biosecurity to prevent H5N1 infection in both poultry and humans.

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Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic Republic

Cited by 93 publications

References 43 publications

Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation

Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation

Molecular epidemiological surveys of H5 subtype highly pathogenic avian influenza viruses in poultry in China during 2007-2009

Genetic characterization of an H5N1 avian influenza virus from a vaccinated duck flock in Vietnam

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