#Environmental #Sampling #Survey of #H5N2 Highly Pathogenic #Avian #Influenza-Infected Layer Chicken #Farms in #Minnesota and #Iowa (Avian Dis., abstract)

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

Avian Dis. 2018 Dec;62(4):373-380. doi: 10.1637/11891-050418-Reg.1.

Environmental Sampling Survey of H5N2 Highly Pathogenic Avian Influenza-Infected Layer Chicken Farms in Minnesota and Iowa.

Lopez KM1, Nezworski J2, Rendahl A1, Culhane M1, Flores-Figueroa C3, Muñoz-Aguayo J3, Halvorson DA1, Johnson R1, Goldsmith T1, Cardona CJ4.

Author information: 1 College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108. 2 Blue House Veterinary, 145 West Yellowstone Trail, Buffalo, MN 55314. 3 Mid-Central Research and Outreach Center, University of Minnesota, 1802 18th St. Northeast, Willmar, MN 56201. 4 College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108, ccardona@umn.edu.

 

Abstract in English, Spanish

Respiratory secretions, feces, feathers, and eggs of avian influenza-infected hens provide ample sources of virus which heavily contaminate barn and farm environments during a disease outbreak. Environmental sampling surveys were conducted in the Midwestern United States on affected farms during the 2015 H5N2 highly pathogenic avian influenza (HPAI) outbreak to assess the degree of viral contamination. A total of 930 samples were obtained from various sites inside and outside layer barns housing infected birds and tested with real-time reverse transcriptase PCR. The distribution and load of viral RNA in barns in which most birds were dead at the onset of depopulation efforts (high-mortality barns) were compared with those of barns in which birds were euthanatized before excess mortality occurred (normal-mortality barns). A statistically significant difference was seen between cycle threshold (Ct) values for samples taken of fans, feed troughs, barn floors, barn walls, cages, manure-associated locations, barn doors, egg belts, and the exterior of high-mortality vs. normal-mortality barns. In high-mortality barns, sample sites were found to be the most to least contaminated in the following order: cages, manure-associated locations, barn floors, egg belts, feed troughs, barn doors, barn walls, fans, exterior, and egg processing. Significant changes in Ct values over time following HPAI detection in a barn and depopulation of birds on an infected farm were observed for the manure-associated, barn floor, barn wall, and fan sampling sites. These results show that high mortality in a flock as a result of HPAI will increase contamination of the farm environment. The results also suggest optimal sampling locations for detection of virus; however, the persistence of RNA on highmortality farms may delay the determination that adequate sanitization has been performed for restocking to take place.

KEYWORDS: barn; contamination; disinfection; egg layers; environmental sampling; highly pathogenic avian influenza; virus

PMID: 31119921 DOI: 10.1637/11891-050418-Reg.1

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

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Estimating within-flock #transmission #rate parameter for #H5N2 highly pathogenic #avian #influenza virus in #Minnesota #turkey flocks during the 2015 #epizootic (Epidemiol Infect., abstract)

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

Epidemiol Infect. 2019 Jan;147:e179. doi: 10.1017/S0950268819000633.

Estimating within-flock transmission rate parameter for H5N2 highly pathogenic avian influenza virus in Minnesota turkey flocks during the 2015 epizootic.

Ssematimba A1, Malladi S1, Hagenaars TJ2, Bonney PJ1, Weaver JT3, Patyk KA3, Spackman E4, Halvorson DA1, Cardona CJ1.

Author information: 1 Secure Food Systems Team,College of Veterinary Medicine,University of Minnesota,1971 Commonwealth Avenue,Saint Paul,MN 55108,USA. 2 Department of Bacteriology and Epidemiology,Wageningen Bioveterinary Research,P.O. Box 65,8200AB Lelystad,The Netherlands. 3 United States Department of Agriculture,Animal and Plant Health Inspection Service, Veterinary Services, Science, Technology, and Analysis Services, Center for Epidemiology and Animal Health, Natural Resources Research Center,Bldg. B MS-2W4, 2150 Centre Avenue, Fort Collins, CO 80526,USA. 4 Exotic and Emerging Avian Viral Diseases Unit,US National Poultry Research Center,USDA-ARS,934 College Station Rd. Athens,GA 30605,USA.

 

Abstract

Better control of highly pathogenic avian influenza (HPAI) outbreaks requires deeper understanding of within-flock virus transmission dynamics. For such fatal diseases, daily mortality provides a proxy for disease incidence. We used the daily mortality data collected during the 2015 H5N2 HPAI outbreak in Minnesota turkey flocks to estimate the within-flock transmission rate parameter (β). The number of birds in Susceptible, Exposed, Infectious and Recovered compartments was inferred from the data and used in a generalised linear mixed model (GLMM) to estimate the parameters. Novel here was the correction of these data for normal mortality before use in the fitting process. We also used mortality threshold to determine HPAI-like mortality to improve the accuracy of estimates from the back-calculation approach. The estimated β was 3.2 (95% confidence interval (CI) 2.3-4.3) per day with a basic reproduction number of 12.8 (95% CI 9.2-17.2). Although flock-level estimates varied, the overall estimate was comparable to those from other studies. Sensitivity analyses demonstrated that the estimated β was highly sensitive to the bird-level latent period, emphasizing the need for its precise estimation. In all, for fatal poultry diseases, the back-calculation approach provides a computationally efficient means to obtain reasonable transmission parameter estimates from mortality data.

KEYWORDS: Analysis of data; avian flu; mathematical modelling; veterinary epidemiology

PMID: 31063119 DOI: 10.1017/S0950268819000633

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

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Age-dependent #pathogenesis of clade 2.3.4.4A #H5N2 #HPAIV in experimentally infected Broad Breasted White #turkeys (Vet Microbiol., abstract)

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

Vet Microbiol. 2019 Apr;231:183-190. doi: 10.1016/j.vetmic.2019.03.011. Epub 2019 Mar 12.

Age-dependent pathogenesis of clade 2.3.4.4A H5N2 HPAIV in experimentally infected Broad Breasted White turkeys.

Carnaccini S1, Santos JJS1, Obadan AO1, Pantin-Jackwood MJ2, Suarez DL2, Rajão DS1, Perez DR3.

Author information: 1 Poultry Diagnostic and Research Center, University of Georgia, College of Veterinary Medicine, 953 College Station Rd, Athens, GA 30602 United States. 2 Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, U.S. Dept. of Agriculture, Agricultural Research Service, 934 College Station Rd., Athens, GA, 30605, United States. 3 Poultry Diagnostic and Research Center, University of Georgia, College of Veterinary Medicine, 953 College Station Rd, Athens, GA 30602 United States. Electronic address: dperez1@uga.edu.

 

Abstract

Highly pathogenic avian influenza (HPAI) is a viral disease with devastating consequences to the poultry industry as it results in high morbidity, mortality and international trade restrictions. In the present study, we characterized age-related differences in terms of pathology in commercial white broad breasted turkeys inoculated with A/turkey/Minnesota/12582/2015 (H5N2) HPAIV clade 2.3.4.4A, a virus from the largest HPAI poultry outbreak that affected the Unites States in 2014-2015. Turkeys infected at 6-weeks of age showed inapparent to little clinical signs with rapid disease progression, reaching 100% mortality at 3 days post infection (dpi). In contrast, turkeys infected at 16-weeks of age developed ataxia and lethargy and reached 100% mortality by 5 dpi. Infection in the 6-weeks old turkeys resulted in peracute lesions consistent of extensive hemorrhages, edema and necrosis, but inflammation was not prominent. In the 16-weeks old turkeys, necrosis and hemorrhages in tissues were accompanied by a more prominent subacute inflammatory infiltrate. Both age groups showed presence of avian influenza virus (AIV) nucleoprotein (NP) in multiple cell types including neurons, glial cells, ependymal cells, respiratory epithelial cells, air capillary epithelium and pulmonary macrophages, cardiac myocytes, smooth muscle fibers, pancreatic acini and ductal cells. Cells of the vascular walls stained strongly positive for viral antigens, but no positivity was found in the endothelial cells of any organs. These findings indicate that age is a determinant factor in the progression of the disease and delay of mortality during infection with the H5N2 clade 2.3.4.4A HPAI virus in naïve white broad breasted turkeys.

Copyright © 2019 Elsevier B.V. All rights reserved.

KEYWORDS: Avian influenza virus; H5N2; HPAI; Immunohistochemistry; Pathogenicity; Turkeys

PMID: 30955808 DOI: 10.1016/j.vetmic.2019.03.011 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N2; Poultry.

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#Shedding of clade 2.3.4.4 #H5N8 and #H5N2 highly pathogenic #avian #influenza viruses in peridomestic #wildbirds in the #US (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Feb 10. doi: 10.1111/tbed.13147. [Epub ahead of print]

Shedding of clade 2.3.4.4 H5N8 and H5N2 highly pathogenic avian influenza viruses in peridomestic wild birds in the U.S.

Bosco-Lauth AM1, Marlenee NL1, Hartwig AE1, Bowen RA1, Root JJ2.

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

 

Abstract

European starlings (Sturnus vulgaris), house sparrows (Passer domesticus) and rock pigeons (Columba livia) are all wild birds commonly found in large numbers in and around human dwellings and domestic livestock operations. This study evaluated the susceptibility of these species to three strains of highly pathogenic avian influenza virus (HP AIV) clade 2.3.4.4 isolated in the US. Experimental infection of European starlings and rock pigeons did not result in any overt signs attributable to AIV infection and no virus shedding was detected from the oral and cloacal routes. House sparrows shed by the oral route and exhibited limited mortality. Individuals from all three species seroconverted following infection. These data suggest that none of these birds are a likely potential bridge host for future HP AIV outbreaks but that their seroconversion may be a useful surveillance tool for detection of circulating H5 HP AIV.

This article is protected by copyright. All rights reserved.

KEYWORDS: Columba livia ; Passer domesticus ; Sturnus vulgaris ; Avian influenza virus; Biosecurity; Clade 2.3.4.4; European starling; Experimental infection; H5N2; H5N8; Highly pathogenic; House sparrow; Outbreak; Rock pigeon

PMID: 30740920 DOI: 10.1111/tbed.13147

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

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#Genetic and biological characterization of two #reassortant #H5N2 #avian #influenza A viruses isolated from #waterfowl in #China in 2016 (Vet Microbiol., abstract)

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

Vet Microbiol. 2018 Oct;224:8-16. doi: 10.1016/j.vetmic.2018.08.016. Epub 2018 Aug 15.

Genetic and biological characterization of two reassortant H5N2 avian influenza A viruses isolated from waterfowl in China in 2016.

Liu K1, Gao R1, Gu M2, Li J1, Shi L1, Sun W1, Liu D1, Gao Z1, Wang X2, Hu J2, Liu X2, Hu S2, Chen S2, Gao S2, Peng D2, Jiao XA2, Liu X3.

Author information: 1 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China. 2 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. 3 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. Electronic address: xfliu@yzu.edu.cn.

 

Abstract

Two reassortant H5N2 viruses in which hemagglutinin (HA) was clustered into clade 2.3.4.4, were isolated from apparently healthy waterfowl in live poultry markets in Eastern China in 2016. We used specific pathogen-free chickens, mallard ducks, and BALB/c mice to evaluate the isolates’ biological characteristics in different animal models. The newly isolated reassortant H5N2 viruses were able to cause severe disease in chickens and effective contact transmission, only at high doses. Our pathogenicity studies in ducks yielded an interesting result: the intravenous pathogenicity index (IVPI) indicated that isolate A/goose/Eastern China/1106/2016(1106) was low pathogenic and the other isolate A/duck/Eastern China/YD1516/2016(YD1516) was of highly pathogenicity in ducks. However, our 50% duck lethal dose (DLD50) experiment demonstrated that these viruses were all of low pathogenicity (DLD50 > 107.0 EID50) in ducks. Additionally, despite the fact that reassortant H5N2 were of low pathogenicity in mice, they could bind to both avian-type (SAα-2,3 Gal) and human-type (SAα-2,6 Gal) receptors, suggesting that these isolates still present a high risk for human infection. Therefore, it is of great importance to implement continual surveillance of avian influenza virus (AIV) to protect both veterinary and public health.

Copyright © 2018 Elsevier B.V. All rights reserved.

KEYWORDS: Avian influenza virus; H5N2; Pathogenicity; Reassortant; Waterfowl

PMID: 30269795 DOI: 10.1016/j.vetmic.2018.08.016 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N2; Reassortant Strain; Wild birds; China.

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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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