scholarly journals Emergence and Selection of a Highly Pathogenic Avian Influenza H7N3 Virus

2020 ◽  
Vol 94 (8) ◽  
Author(s):  
Nancy Beerens ◽  
Rene Heutink ◽  
Frank Harders ◽  
Alex Bossers ◽  
Guus Koch ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Cleavage Site ◽  
Highly Pathogenic Avian Influenza ◽  
Severe Disease ◽  
Virus Population ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
High Pathogenicity ◽  
H7n3 Virus ◽  
Selection Of

ABSTRACT 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.

scholarly journals Highly Pathogenic Avian Influenza A(H7N3) Virus in Poultry Workers, Mexico, 2012

2013 ◽  
Vol 19 (9) ◽  
Author(s):  
Irma Lopez-Martinez ◽  
Amanda Balish ◽  
Gisela Barrera-Badillo ◽  
Joyce Jones ◽  
Tatiana E. Nuñez-García ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Highly Pathogenic Avian Influenza ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Poultry Workers ◽  
H7n3 Virus

scholarly journals The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 920
Author(s):  
Amanda Seekings ◽  
Wendy Howard ◽  
Alejandro Nuñéz ◽  
Marek Slomka ◽  
Ashley Banyard ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Cleavage Site ◽  
Highly Pathogenic Avian Influenza ◽  
Basic Amino Acid ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Pathogenic Avian Influenza Virus

Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7DB), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7SB). Passage of H7N7DB in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7SB was serially passaged showed retention of the LPAIV genotype. Thus, in chicken embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in embryo tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV.

scholarly journals Unexpected Interfarm Transmission Dynamics during a Highly Pathogenic Avian Influenza Epidemic

2016 ◽  
Vol 90 (14) ◽  
pp. 6401-6411 ◽  
Author(s):  
Alice Fusaro ◽  
Luca Tassoni ◽  
Adelaide Milani ◽  
Joseph Hughes ◽  
Annalisa Salviato ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Avian Influenza ◽  
Cleavage Site ◽  
Highly Pathogenic Avian Influenza ◽  
Index Case ◽  
Genetic Data ◽  
Transmission Dynamics ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Naturally Occurring

ABSTRACTNext-generation sequencing technology is now being increasingly applied to study the within- and between-host population dynamics of viruses. However, information on avian influenza virus evolution and transmission during a naturally occurring epidemic is still limited. Here, we use deep-sequencing data obtained from clinical samples collected from five industrial holdings and a backyard farm infected during the 2013 highly pathogenic avian influenza (HPAI) H7N7 epidemic in Italy to unravel (i) the epidemic virus population diversity, (ii) the evolution of virus pathogenicity, and (iii) the pathways of viral transmission between different holdings and sheds. We show a high level of genetic diversity of the HPAI H7N7 viruses within a single farm as a consequence of separate bottlenecks and founder effects. In particular, we identified the cocirculation in the index case of two viral strains showing a different insertion at the hemagglutinin cleavage site, as well as nine nucleotide differences at the consensus level and 92 minority variants. To assess interfarm transmission, we combined epidemiological and genetic data and identified the index case as the major source of the virus, suggesting the spread of different viral haplotypes from the index farm to the other industrial holdings, probably at different time points. Our results revealed interfarm transmission dynamics that the epidemiological data alone could not unravel and demonstrated that delay in the disease detection and stamping out was the major cause of the emergence and the spread of the HPAI strain.IMPORTANCEThe within- and between-host evolutionary dynamics of a highly pathogenic avian influenza (HPAI) strain during a naturally occurring epidemic is currently poorly understood. Here, we perform for the first time an in-depth sequence analysis of all the samples collected during a HPAI epidemic and demonstrate the importance to complement outbreak investigations with genetic data to reconstruct the transmission dynamics of the viruses and to evaluate the within- and between-farm genetic diversity of the viral population. We show that the evolutionary transition from the low pathogenic form to the highly pathogenic form occurred within the first infected flock, where we identified haplotypes with hemagglutinin cleavage site of different lengths. We also identify the index case as the major source of virus, indicating that prompt application of depopulation measures is essential to limit virus spread to other farms.

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