Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs

AbstractH9N2 is the most prevalent low pathogenic avian influenza virus (LPAIV) in domestic poultry in the world. Two distinct H9N2 poultry lineages, G1-like (A/quail/Hong Kong/G1/97) and Y280-like (A/Duck/Hong Kong/Y280/1997) viruses, are usually associated with binding affinity for both α 2,3 and α 2,6 sialic acid receptors (avian and human receptors), raising concern whether these viruses possess pandemic potential. To explore the impact of mouse adaptation on the transmissibility of a Y280-like virus A/Chicken/Hubei/214/2017(H9N2) (abbreviated as WT), we performed serial lung-to-lung passages of the WT virus in mice. The mouse-adapted variant (MA) exhibited enhanced pathogenicity and advantaged transmissibility after passaging in mice. Sequence analysis of the complete genomes of the MA virus revealed a total of 16 amino acid substitutions. These mutations distributed across 7 segments including PB2, PB1, PA, NP, HA, NA and NS1 genes. Furthermore, we generated a panel of recombinant or mutant H9N2 viruses using reverse genetics technology and confirmed that the PB2 gene governing the increased pathogenicity and transmissibility. The combinations of 340 K and 588 V in PB2 were important in determining the altered features. Our findings elucidate the specific mutations in PB2 contribute to the phenotype differences and emphasize the importance of monitoring the identified amino acid substitutions due to their potential threat to human health.

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Amino acid substitutions in low pathogenic avian influenza virus strains isolated from wild birds in Korea

Virus Genes ◽

10.1007/s11262-018-1550-7 ◽

2018 ◽

Vol 54 (3) ◽

pp. 397-405 ◽

Cited By ~ 2

Author(s):

Kwang-Hyun Oh ◽

Jong-Suk Mo ◽

Yeon-Ji Bae ◽

Seung-Baek Lee ◽

Van Dam Lai ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Wild Birds ◽

Amino Acid Substitutions ◽

Pathogenic Avian Influenza ◽

Pathogenic Avian Influenza Virus ◽

Low Pathogenic Avian Influenza ◽

Virus Strains

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Characterization of H9N2 influenza A viruses isolated from chicken products imported into Japan from China

Epidemiology and Infection ◽

10.1017/s0950268806006728 ◽

2006 ◽

Vol 135 (3) ◽

pp. 386-391 ◽

Cited By ~ 13

Author(s):

M. MASE ◽

M. ETO ◽

K. IMAI ◽

K. TSUKAMOTO ◽

S. YAMAGUCHI

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Influenza A ◽

H9n2 Virus ◽

Amino Acid Substitutions ◽

Influenza A Viruses ◽

Potential Sources

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.

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Multiple amino acid substitutions are involved in the adaptation of H9N2 avian influenza virus to mice

Veterinary Microbiology ◽

10.1016/j.vetmic.2009.03.010 ◽

2009 ◽

Vol 138 (1-2) ◽

pp. 85-91 ◽

Cited By ~ 43

Author(s):

Rui Wu ◽

Hongbo Zhang ◽

Keli Yang ◽

Wangwang Liang ◽

Zhongliang Xiong ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Amino Acid Substitutions ◽

H9n2 Avian Influenza Virus ◽

Multiple Amino Acid

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Molecular analysis of highly pathogenic avian influenza virus of subtype H5N1 isolated from wild birds and mammals in northern Germany

Journal of General Virology ◽

10.1099/vir.0.82300-0 ◽

2007 ◽

Vol 88 (2) ◽

pp. 554-558 ◽

Cited By ~ 69

Author(s):

Siegfried Weber ◽

Timm Harder ◽

Elke Starick ◽

Martin Beer ◽

Ortrud Werner ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Wild Bird ◽

Highly Pathogenic Avian Influenza ◽

Highly Pathogenic ◽

Pathogenic Avian Influenza ◽

H5n1 Isolate ◽

Pathogenic Avian Influenza Virus

Analysis of the full-length sequences of all eight segments of the German wild-bird H5N1 highly pathogenic avian influenza virus index isolate, A/Cygnus cygnus/Germany/R65/2006, and an H5N1 isolate from a cat (A/cat/Germany/R606/2006) obtained during an outbreak in February 2006 revealed a very high similarity between these two sequences. One amino acid substitution in the PA gene, encoding a protein involved in virus RNA replication, and one amino acid substitution in the haemagglutinin (HA) protein were observed. Phylogenetic analyses of the HA and neuraminidase nucleotide sequences showed that avian influenza H5N1 isolates from the Astrakhan region located in southern Russia were the closest relatives. Reassortment events could be excluded in comparison with other ‘Qinghai-like’ H5N1 viruses. In addition, an H5N1 isolate originating from a single outbreak in poultry in Germany was found to be related closely to the H5N1 viruses circulating at that time in the wild-bird population.

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Amino acid substitutions in the neuraminidase protein of an H9N2 avian influenza virus affect its airborne transmission in chickens

Veterinary Research ◽

10.1186/s13567-014-0142-3 ◽

2015 ◽

Vol 46 (1) ◽

Cited By ~ 12

Author(s):

Jing Lv ◽

Liangmeng Wei ◽

Yan Yang ◽

Bingxiao Wang ◽

Wei Liang ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Amino Acid Substitutions ◽

Airborne Transmission ◽

H9n2 Avian Influenza Virus

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

Viruses ◽

10.3390/v12090920 ◽

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.

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