T160A #mutation-induced deglycosylation at site 158 in #HA is a critical determinant of the dual #RB properties of clade 2.3.4.4 #H5NX subtype #avian #influenza viruses (Vet Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Microbiol. 2018 Apr;217:158-166. doi: 10.1016/j.vetmic.2018.03.018. Epub 2018 Mar 17.

T160A mutation-induced deglycosylation at site 158 in hemagglutinin is a critical determinant of the dual receptor binding properties of clade 2.3.4.4 H5NX subtype avian influenza viruses.

Gao R1, Gu M2, Liu K1, Li Q1, Li J1, Shi L1, Li X1, Wang X2, Hu J2, Liu X2, Hu S2, Chen S2, Peng D3, Jiao X3, Liu X4.

Author information: 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China. 2 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China. 3 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, Jiangsu 225009, China. 4 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, Jiangsu 225009, China. Electronic address: xfliu@yzu.edu.cn.

 

Abstract

Most clade 2.3.4.4 H5NX subtype avian influenza viruses possess a T160A amino acid substitution in the hemagglutinin (HA) protein that has been shown to affect the receptor binding properties of a clade 2.3.4 H5N1 virus. However, the effect of this single site mutation on the HA backbone of clade 2.3.4.4 H5NX viruses remains unclear. In this study, two H5N6 field isolates possessing HA-160A with dual α-2,3 and α-2,6 receptor binding properties (Y6 virus) and HA-160T with α-2,3 receptor binding affinity (HX virus), respectively, were selected to generate HA mutants containing all of the internal genes from A/PR8/H1N1 virus for comparative investigation. We found that the Y6-P-160A and RHX-P-160A viruses each with 160A in the HA resulting in loss of glycosylation at site 158 exhibited binding to the two receptor types, whereas the RY6-P-160T and HX-P-160T viruses each with 160T in the HA displayed selective binding to α-2,3 receptors only. In addition, differences were noted in the replication of these four H5N6 recombinants in avian and mammalian cells, as well as in their pathogenicity in mice. The contribution of deglycosylation at site 158 to the acquisition of human-like receptors was further verified in H5N2, H5N5 and H5N8 reassortants. Therefore, we conclude that the lack of glycosylation at site 158 induced by the T160A mutation in HA is a critical determinant for the dual receptor binding properties of clade 2.3.4.4 H5NX viruses. This new insight may be helpful in assessing the pandemic potential of novel H5 isolates.

KEYWORDS: 158; Clade 2.3.4.4; Glycosylation; H5NX; Receptor

PMID: 29615249 DOI: 10.1016/j.vetmic.2018.03.018 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N2; H5N5; H5N6; H5N8; Reassortant Strain.

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In vitro characterization of #baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the #influenza virus #polymerase PA subunit (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res. 2018 Oct 11. pii: S0166-3542(18)30363-2. doi: 10.1016/j.antiviral.2018.10.008. [Epub ahead of print]

In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit.

Noshi T1, Kitano M1, Taniguchi K2, Yamamoto A1, Omoto S1, Baba K1, Hashimoto T1, Ishida K1, Kushima Y1, Hattori K1, Kawai M1, Yoshida R1, Kobayashi M1, Yoshinaga T1, Sato A3, Okamatsu M4, Sakoda Y4, Kida H5, Shishido T6, Naito A1.

Author information: 1 Shionogi & Co., Ltd, Osaka, Japan. 2 Shionogi & Co., Ltd, Osaka, Japan; Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Japan. 3 Shionogi & Co., Ltd, Osaka, Japan; Research Center for Zoonosis Control, Hokkaido University, Japan. 4 Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Japan. 5 Research Center for Zoonosis Control, Hokkaido University, Japan. 6 Shionogi & Co., Ltd, Osaka, Japan. Electronic address: takao.shishido@shionogi.co.jp.

 

Abstract

Cap-dependent endonuclease (CEN) resides in the PA subunit of the influenza virus and mediates the critical “cap-snatching” step of viral RNA transcription, which is considered to be a promising anti-influenza target. Here, we describe in vitro characterization of a novel CEN inhibitor, baloxavir acid (BXA), the active form of baloxavir marboxil (BXM). BXA inhibits viral RNA transcription via selective inhibition of CEN activity in enzymatic assays, and inhibits viral replication in infected cells without cytotoxicity in cytopathic effect assays. The antiviral activity of BXA is also confirmed in yield reduction assays with seasonal type A and B viruses, including neuraminidase inhibitor-resistant strains. Furthermore, BXA shows broad potency against various subtypes of influenza A viruses (H1N2, H5N1, H5N2, H5N6, H7N9 and H9N2). Additionally, serial passages of the viruses in the presence of BXA result in isolation of PA/I38T variants with reduced BXA susceptibility. Phenotypic and genotypic analyses with reverse genetics demonstrate the mechanism of BXA action via CEN inhibition in infected cells. These results reveal the in vitro characteristics of BXA and support clinical use of BXM to treat influenza.

KEYWORDS: Baloxavir acid; Baloxavir marboxil; Cap-dependent endonuclease; Influenza virus

PMID: 30316915 DOI: 10.1016/j.antiviral.2018.10.008

Keywords: Influenza A; Influenza B; H1N1pdm09; H3N2; H1N2; H5N1; H5N6; H7N9; H9N2; H5N2; Antivirals; Baloxavir.

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Spatial #transmission of #H5N2 highly pathogenic #avian #influenza between #Minnesota #poultry premises during the 2015 #outbreak (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Spatial transmission of H5N2 highly pathogenic avian influenza between Minnesota poultry premises during the 2015 outbreak

Peter J. Bonney , Sasidhar Malladi, Gert Jan Boender, J. Todd Weaver, Amos Ssematimba, David A. Halvorson, Carol J. Cardona

Published: September 21, 2018 / DOI: https://doi.org/10.1371/journal.pone.0204262

 

Abstract

The spatial spread of highly pathogenic avian influenza (HPAI) H5N2 during the 2015 outbreak in the U.S. state of Minnesota was analyzed through the estimation of a spatial transmission kernel, which quantifies the infection hazard an infectious premises poses to an uninfected premises some given distance away. Parameters were estimated using a maximum likelihood method for the entire outbreak as well as for two phases defined by the daily number of newly detected HPAI-positive premises. The results indicate both a strong dependence of the likelihood of transmission on distance and a significant distance-independent component of outbreak spread for the overall outbreak. The results further suggest that HPAI spread differed during the later phase of the outbreak. The estimated spatial transmission kernel was used to compare the Minnesota outbreak with previous HPAI outbreaks in the Netherlands and Italy to contextualize the Minnesota transmission kernel results and make additional inferences about HPAI transmission during the Minnesota outbreak. Lastly, the spatial transmission kernel was used to identify high risk areas for HPAI spread in Minnesota. Risk maps were also used to evaluate the potential impact of an early marketing strategy implemented by poultry producers in a county in Minnesota during the outbreak, with results providing evidence that the strategy was successful in reducing the potential for HPAI spread.

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Citation: Bonney PJ, Malladi S, Boender GJ, Weaver JT, Ssematimba A, Halvorson DA, et al. (2018) Spatial transmission of H5N2 highly pathogenic avian influenza between Minnesota poultry premises during the 2015 outbreak. PLoS ONE 13(9): e0204262. https://doi.org/10.1371/journal.pone.0204262

Editor: Huaijun Zhou, University of California Davis, UNITED STATES

Received: May 7, 2018; Accepted: September 4, 2018; Published: September 21, 2018

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: The data underlying the findings of this study are not publicly available due to legal and security concerns. Requests for access may be made by email to Dr. Jonathan Zack of the United States Department of Agriculture; Animal and Plant Health Inspection Service; Veterinary Services; Surveillance, Preparedness, and Response Services at jonathan.t.zack@aphis.usda.gov.

Funding: This work was completed under the cooperative agreement between the United States Department of Agriculture, Animal Plant Health Inspection Service, Veterinary Services and the University of Minnesota for risk assessments to support national preparedness planning for animal health emergencies (14-9208-0365CA). Authors who received this funding include PB, SM, AS, DH, and CC. The funders reviewed the manuscript prior to publication.

Competing interests: The authors have declared that no competing interests exist.

Keywords: H5N2; Avian Influenza; Poultry; USA; Minnesota.

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Novel #reassortant #H5N6 highly pathogenic #influenza A viruses in #Vietnamese #quail #outbreaks (Comp Immunol Microbiol Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Comp Immunol Microbiol Infect Dis. 2018 Feb;56:45-57. doi: 10.1016/j.cimid.2018.01.001. Epub 2018 Jan 10.

Novel reassortant H5N6 highly pathogenic influenza A viruses in Vietnamese quail outbreaks.

Thanh HD1, Tran VT2, Nguyen DT3, Hung VK3, Kim W4.

Author information: 1 Department of Microbiology, Chung-Ang University, College of Medicine, Seoul, South Korea; Central Vietnam Veterinary Institute, Nha Trang, Viet Nam. 2 Department of Microbiology, Chung-Ang University, College of Medicine, Seoul, South Korea. 3 Central Vietnam Veterinary Institute, Nha Trang, Viet Nam. 4 Department of Microbiology, Chung-Ang University, College of Medicine, Seoul, South Korea. Electronic address: kimwy@cau.ac.kr.

 

Abstract

Avian influenza A H5N6 virus is a highly contagious infectious agent that affects domestic poultry and humans in South Asian countries. Vietnam may be an evolutionary hotspot for influenza viruses and therefore could serve as a source of pandemic strains. In 2015, two novel reassortant H5N6 influenza viruses designated as A/quail/Vietnam/CVVI01/2015 and A/quail/Vietnam/CVVI03/2015 were isolated from dead quails during avian influenza outbreaks in central Vietnam, and the whole genome sequences were analyzed. The genetic analysis indicated that hemagglutinin, neuraminidase, and polymerase basic protein 2 genes of the two H5N6 viruses are most closely related to an H5N2 virus (A/chicken/Zhejiang/727079/2014) and H10N6 virus (A/chicken/Jiangxi/12782/2014) from China and an H6N6 virus (A/duck/Yamagata/061004/2014) from Japan. The HA gene of the isolates belongs to clade 2.3.4.4, which caused human fatalities in China during 2014-2016. The five other internal genes showed high identity to an H5N2 virus (A/chicken/Heilongjiang/S7/2014) from China. A whole-genome phylogenetic analysis revealed that these two outbreak strains are novel H6N6-like PB2 gene reassortants that are most closely related to influenza virus strain A/environment/Guangdong/ZS558/2015, which was detected in a live poultry market in China. This report describes the first detection of novel H5N6 reassortants in poultry during an outbreak as well as genetic characterization of these strains to better understand the antigenic evolution of influenza viruses.

KEYWORDS: Avian influenza A virus; H5N6; Vietnam

PMID: 29406283 DOI: 10.1016/j.cimid.2018.01.001 [Indexed for MEDLINE]

Keywords: Avian Influenza; Reassortant Strain; Poultry; Vietnam; H5N6; H5N2; H6N6; H10N6.

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Molecular #Phylogenetic Analysis of a Highly Pathogenic #H5N2 #Avian #Influenza Virus Isolated from #Duck (Bing Du Xue Bao, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Bing Du Xue Bao. 2016 Sep;32(5):590-6.

[Molecular Phylogenetic Analysis of a Highly Pathogenic H5N2 Avian Influenza Virus Isolated from Duck].

[Article in Chinese]

Yao Y, He B, Shao Z, Yang W, Liu W, Chen X, Ye S, Chen J.

 

Abstract

In 2016,routine influenza virus surveillance was conducted in the live poultry markets of Wuhan, Hubei Province. An H5N2 subtype avian influenza virus(AIV)was isolated from ducks in Wuhan. The entire genome of this virus isolate was sequenced,and molecular phylogenetic analysis performed. The results indicated that the HA gene belonged to clade 2.3.4.4and contained multiple basic amino acids at the cleavage site, which is characteristic of highly pathogenic AIV. Sequence alignment revealed that the isolate shared a high degree of homology with different H5 subtype AIVs isolated from waterfowl in southern China in recent years. This isolate was likely a natural reassortant from different subtype AIVs. This study provides epidemiological evidence of influenza evolution. Continuation of molecular epidemiology studies of H5 subtype influenza viruses in live poultry markets is important for understanding their role in the variation and evolution of highly pathogenic AIVs and their potential hazardous effects on human health. Furthermore, this information is important for strengthening comprehensive AIV surveillance and control measures.

PMID: 30001581 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N2; Reassortant Strain; Poultry; Live Poultry Markets; China.

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Viral shedding of clade 2.3.4.4 #H5 highly pathogenic #avian #influenza A viruses by American #robins (Transbound Emerg Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Transbound Emerg Dis. 2018 Jul 17. doi: 10.1111/tbed.12959. [Epub ahead of print]

Viral shedding of clade 2.3.4.4 H5 highly pathogenic avian influenza A viruses by American robins.

Root JJ1, Bosco-Lauth AM2, Marlenee NL2, Bowen RA2.

Author information: 1 United States Department of Agriculture, National Wildlife Research Center, Fort Collins, Colorado. 2 Colorado State University, Fort Collins, Colorado.

 

Abstract

American robins (Turdus migratorius) are commonly associated with farmsteads in the United States and have shown previous evidence of exposure to an H5 avian influenza A virus (IAV) near a poultry production facility affected by a highly pathogenic (HP) H5 virus in Iowa, USA during 2015. We experimentally infected American robins with three clade 2.3.4.4 HP H5 viruses (H5N2 and H5N8). A total of 22/24 American robins shed virus, and all three strains were represented. The highest virus titres shed were 104.3 , 104.3 and 104.8 PFU/ml, associated respectively with viruses isolated from poultry, a captive gyrfalcon (Falco rusticolus), and a Northern pintail (Anas acuta). Of those birds that shed, viral shedding was initiated 1 or 2 days post-infection (DPI) and shedding ceased in all birds by 7 DPI. This study adds an additional synanthropic wildlife species to a growing list of animals that can successfully replicate and shed IAVs.

KEYWORDS: Turdus migratorius ; American robin; Avian influenza A virus; Biosecurity; Clade 2.3.4.4; Experimental infection; H5N2; H5N8; Highly pathogenic; Outbreak; Passerine

PMID: 30014592 DOI: 10.1111/tbed.12959

Keywords: Avian Influenza; H5N2; H5N8; Wild Birds; USA.

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Compatibility between #haemagglutinin and #neuraminidase drives the recent emergence of novel clade 2.3.4.4 #H5Nx #avian #influenza viruses in #China (Transbound Emerg Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Transbound Emerg Dis. 2018 Jul 12. doi: 10.1111/tbed.12949. [Epub ahead of print]

Compatibility between haemagglutinin and neuraminidase drives the recent emergence of novel clade 2.3.4.4 H5Nx avian influenza viruses in China.

Qin T1,2,3,4, Zhu J1,2,3,4, Ma R1,2,3,4, Yin Y1,2,3,4, Chen S1,2,3,4, Peng D1,2,3,4, Liu X1,2,3,4.

Author information: 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, China. 2 Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, China. 3 Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease, Yangzhou, China. 4 Joint Laboratory Safety of International Cooperation of Agriculture & Agricultural-Products, Yangzhou, China.

 

Abstract

Genetic reassortments between highly pathogenic avian influenza (HPAI) H5 subtype viruses with different neuraminidase (NA) subtypes have increased in prevalence since 2010 in wild birds and poultry from China. The HA gene slightly evolved from clade 2.3.4 to clade 2.3.4.4, raising the question of whether novel clade 2.3.4.4 HA broke the balance with N1 but is matched well with NAx to drive viral epidemics. To clarify the role of compatibility between HA and NA on the prevalence of H5Nx subtypes, we constructed 10 recombinant viruses in which the clade 2.3.4 or clade 2.3.4.4 HA genes were matched with different NA (N1, N2 and N8) genes and evaluated viral characteristics and pathogenicity. Combinations between clade 2.3.4 HA and N1 or between clade 2.3.4.4 HA and NAx, but not between clade 2.3.4.4 HA and N1, or between clade 2.3.4 HA and NAx, promoted viral growth, NA activity, thermostability, low-pH stability and pathogenicity in chicken and mice. These findings suggest that both clade 2.3.4 HA/N1 and clade 2.3.4.4 HA/NAx displayed a better match, which could promote the increased prevalence of clade 2.3.4 H5N1 AIV (prior to 2010) and clade 2.3.4.4 H5Nx AIV (since 2010) in China, respectively.

KEYWORDS: avian influenza viruses; clade 2.3.4.4 H5Nx virus; compatibility

PMID: 29999588 DOI: 10.1111/tbed.12949

Keywords: Avian Influenza; H5N1; H5N6; H5N8; Poultry; China.

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