Dataset Information

Emergence of mammalian species-infectious and -pathogenic avian influenza H6N5 virus with no evidence of adaptation.

ABSTRACT: 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.

SUBMITTER: Nam JH

PROVIDER: S-EPMC3233153 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Emergence of mammalian species-infectious and -pathogenic avian influenza H6N5 virus with no evidence of adaptation.

Nam Jeong-Hyun JH Kim Eun-Ha EH Song Daesub D Choi Young Ki YK Kim Jeong-Ki JK Poo Haryoung H

Journal of virology 20111012 24

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 isol ...[more]

PMID: 21994462

Similar Datasets

Project description:Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high- and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties.The Italian H7 AI epidemic of 1999 to 2001 was one of the most important AI outbreaks described in Europe. H7 viruses have the ability to evolve into HP forms from LP precursors, although the mechanisms underlying this evolutionary transition are only poorly understood. We combined epidemiological information, whole-genome sequence data, and ultradeep sequencing approaches to provide the most complete characterization of the evolution of HPAI from LPAI viruses undertaken to date. Our analysis revealed that the LPAI viruses were the direct ancestors of the HPAI strains and identified low-frequency minority variants with HPAI mutations that were present in the LPAI samples. Spatial analysis provided key information for the design of effective control strategies for AI at both local and global scales. Overall, this work highlights the importance of implementing rapid eradication measures to prevent the emergence of novel influenza viruses with severe pathogenic properties.

Project description:Low-pathogenicity avian influenza (LPAI) viruses of subtypes H5 and H7 have the ability to spontaneously mutate to highly pathogenic (HPAI) virus variants, causing high mortality in poultry. The highly pathogenic phenotype is caused by mutation of the hemagglutinin (HA) cleavage site, but additional mutations may play a role. Evidence from the field for the switch to high pathogenicity remains scarce. This study provides direct evidence for LPAI-to-HPAI virus mutation during H7N3 infection of a turkey farm in the Netherlands. No severe clinical symptoms were reported at the farm, but deep sequencing of isolates from the infected turkeys revealed a minority of HPAI virus sequences (0.06%) in the virus population. The HPAI virus contained a 12-nucleotide insertion in the HA cleavage site that was likely introduced by a single event as no intermediates with shorter inserts were identified. This suggests nonhomologous recombination as the mechanism of insertion. Analysis of different organs of the infected turkeys showed the largest amount of HPAI virus in the lung (4.4%). The HPAI virus was rapidly selected in experimentally infected chickens after both intravenous and intranasal/intratracheal inoculation with a mixed virus preparation. Full-genome sequencing revealed that both pathotypes contained a deletion in the stalk region of the neuraminidase protein. We identified additional mutations in HA and polymerase basic protein 1 (PB1) in the HPAI virus, which were already present as minority variants in the LPAI virus population. Our findings provide more insight into the molecular changes and mechanisms involved in the emergence and selection of HPAI viruses.IMPORTANCE Low-pathogenicity avian influenza (LPAI) viruses circulate in wild birds and can be transmitted to poultry. LPAI viruses can mutate to become highly pathogenic avian influenza (HPAI) viruses causing severe disease and death in poultry. Little is known about this switch to high pathogenicity. We isolated an LPAI H7N3 virus from an infected turkey farm and showed that this contains small amounts of HPAI virus. The HPAI virus rapidly outcompeted the LPAI virus in chickens that were experimentally infected with this mixture of viruses. We analyzed the genome sequences of the LPAI and HPAI viruses and identified several changes that may be important for a virus to become highly pathogenic. This knowledge may be used for timely identification of LPAI viruses that pose a risk of becoming highly pathogenic in the field.

Project description:Influenza A viruses (IAVs) are common pathogens of birds that occasionally establish endemic infections in mammals. The processes and mechanisms that result in IAV mammalian adaptation are poorly understood. The viral nonstructural 1 (NS1) protein counteracts the interferon (IFN) response, a central component of the host species barrier. We characterized the NS1 proteins of equine influenza virus (EIV), a mammalian IAV lineage of avian origin. We showed that evolutionarily distinct NS1 proteins counteract the IFN response using different and mutually exclusive mechanisms: while the NS1 proteins of early EIVs block general gene expression by binding to cellular polyadenylation-specific factor 30 (CPSF30), NS1 proteins from more evolved EIVs specifically block the induction of IFN-stimulated genes by interfering with the JAK/STAT pathway. These contrasting anti-IFN strategies are associated with two mutations that appeared sequentially and were rapidly selected for during EIV evolution, highlighting the importance of evolutionary processes in immune evasion mechanisms during IAV adaptation.IMPORTANCE Influenza A viruses (IAVs) infect certain avian reservoir species and occasionally transfer to and cause epidemics of infections in some mammalian hosts. However, the processes by which IAVs gain the ability to efficiently infect and transmit in mammals remain unclear. H3N8 equine influenza virus (EIV) is an avian-origin virus that successfully established a new lineage in horses in the early 1960s and is currently circulating worldwide in the equine population. Here, we analyzed the molecular evolution of the virulence factor nonstructural protein 1 (NS1) and show that NS1 proteins from different time periods after EIV emergence counteract the host innate immune response using contrasting strategies, which are associated with two mutations that appeared sequentially during EIV evolution. The results shown here indicate that the interplay between virus evolution and immune evasion plays a key role in IAV mammalian adaptation.

Dataset Information

Emergence of mammalian species-infectious and -pathogenic avian influenza H6N5 virus with no evidence of adaptation.

Publications

Emergence of mammalian species-infectious and -pathogenic avian influenza H6N5 virus with no evidence of adaptation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets