Treatment of Highly Pathogenic #H7N9 Virus-Infected Mice with #Baloxavir Marboxil (Viruses, abstract)

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

Viruses. 2019 Nov 15;11(11). pii: E1066. doi: 10.3390/v11111066.

Treatment of Highly Pathogenic H7N9 Virus-Infected Mice with Baloxavir Marboxil.

Kiso M1, Yamayoshi S1, Furusawa Y1, Imai M1, Kawaoka Y1,2,3.

Author information: 1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. 2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA. 3 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.

 

Abstract

Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.

KEYWORDS: H7N9; baloxavir marboxil; highly pathogenic; influenza

PMID: 31731678 DOI: 10.3390/v11111066

Keywords: Antivirals; Avian Influenza; H7N9; Baloxavir Marboxil; Animal models.

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Comparative #Pathogenicity and #Transmissibility of the #H7N9 Highly Pathogenic #Avian #Influenza Virus and the H7N9 LPAI Virus in #Chickens (Viruses, abstract)

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

Viruses. 2019 Nov 10;11(11). pii: E1047. doi: 10.3390/v11111047.

Comparative Pathogenicity and Transmissibility of the H7N9 Highly Pathogenic Avian Influenza Virus and the H7N9 Low Pathogenic Avian Influenza Virus in Chickens.

Yu H1, Zhang K1, Ye X1, Wang W1, Wu W1, Wang X1, Guan Y1, He Z1, Wang Y2, Jiao P1.

Author information: 1 College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Tianhe District, Guangzhou 510642, China. 2 Department of Epidemiology, Public Health College, Harbin Medical University, Harbin 150081, China.

 

Abstract

There were five outbreaks of H7N9 influenza virus in humans in China since it emerged in 2013, infecting >1000 people. The H7N9 low pathogenic influenza virus was inserted into four amino acids in the HA protein cleavage site to mutate into the H7N9 highly pathogenic virus. This emerging virus caused 15 outbreaks in chickens from the end of 2016 to date. Two H7N9 avian influenza virus (AIV) strains, A/chicken/Guangdong/A46/2013 (LPAIV) and A/chicken/Guangdong/Q29/2017 (HPAIV), were selected to compare the pathogenicity and transmissibility between H7N9 LPAIVs and HPAIVs in chickens. We inoculated 3- to 4-week-old specific-pathogen-free (SPF) chickens with 6 log10EID50/0.1 mL viruses via the ocular-nasal route and co-housed four chickens in each group. The inoculated chicken mortality rate in the A46 and Q29 groups was 1/5 and 5/5, respectively. Q29 virus replication was more efficient compared to the A46 virus in inoculated chickens. Infected chickens initiated viral shedding to naïve contact chickens through respiratory and digestive routes. Both viruses transmitted between chickens by naïve contact, but the Q29 virus had a higher pathogenicity in contact chickens than the A46 virus. Compared with early H7N9 LPAIVs, the pathogenicity and transmissibility of the emerging H7N9 HPAIV was stronger in chickens, indicating that H7N9 influenza virus may continue to threaten human and poultry health.

KEYWORDS: H7N9; avian influenza virus; chickens; pathogenicity; transmissibility

PMID: 31717632 DOI: 10.3390/v11111047

Keywords: Avian Influenza; H7N9; Poultry.

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#Characteristics of #H7N9 #avian #influenza #pneumonia: a retrospective analysis of 17 cases (Inter Med J., abstract)

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

Intern Med J. 2019 Nov 10. doi: 10.1111/imj.14685. [Epub ahead of print]

Characteristics of H7N9 avian influenza pneumonia: a retrospective analysis of 17 cases.

Yu WQ1,2, Ji NF1, Ding MD2, Gu CJ3, Ma Y1, Wu ZZ1, Wang YL1, Wu CJ1, Dai GH4, Chen Y4, Jin RR4, Tan YB5, Yang Z6, Zhou DM2, Xian JC2, Xu HT2, Huang M1.

Author information: 1 Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. 2 Department of Infectious Diseases, Taizhou People’s hospital, Taizhou, 225300, China. 3 Department of Pharmacy, Taizhou People’s hospital, Taizhou, 225300, China. 4 Department of Pathology, Taizhou People’s hospital, Taizhou, 225300, China. 5 Department of Nuclear Medicine, Taizhou People’s hospital, Taizhou, 225300, China. 6 Department of Medical Microbiology and Immunology, Wannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, Anhui, 241002, China.

 

Abstract

BACKGROUND:

H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential.

OBJECTIVES:

We aimed to describe the clinical features of H7N9 avian influenza and the response to treatment.

METHODS:

Clinical, radiological, and histopathological data, and treatment-related of H7N9-infected patients hospitalized during 2014-2017 were extracted and analyzed.

RESULTS:

A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) were identified; of these six died. All patients presented with fever and productive cough; four patients had hemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground-glass opacities, air bronchograms, and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype, while the others had the C/T genotype.

CONCLUSIONS:

H7N9 virus infection causes human influenza-like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high-risk patients. The presence of the IFITM3 rs12252-C genotype may predict severe illness.

This article is protected by copyright. All rights reserved.

PMID: 31707755 DOI: 10.1111/imj.14685

Keywords: Avian Influenza; H7N9; Human; China; Genetics.

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The #aminoacid #mutations A286V and T437M in the #nucleoprotein attenuate #H7N9 viruses in mice (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

The amino acid mutations A286V and T437M in the nucleoprotein attenuate H7N9 viruses in mice

Shujie Ma, Bo Zhang, Jianzhong Shi, Xin Yin, Guangwen Wang, Pengfei Cui, Liling Liu, Guohua Deng, Yongping Jiang, Chengjun Li, Hualan Chen

DOI: 10.1128/JVI.01530-19

 

ABSTRACT

The low pathogenic H7N9 influenza viruses that emerged in 2013 acquired an insertion of four amino acids in their hemagglutinin cleavage site and thereby became highly pathogenic to chickens in 2017. Previous studies indicate that these highly pathogenic H7N9 viruses are virulent in chickens but have distinct pathotypes in mice. A/chicken/Guangdong/SD098 (CK/SD098) is avirulent with a mouse lethal dose (MLD50) greater than 7.5 log10 50% egg infectious dose (EID50), whereas A/chicken/Hunan/S1220 (CK/S1220) is virulent in mice with an MLD50 of 3.2 log10 EID50. In this study, we explored the genetic determinants that contribute to the difference in virulence between these two H7N9 viruses by generating a series of reassortants and mutants in the CK/S1220 virus background and testing their virulence in mice. We found that the reassortant CK/1220-SD098-NP carrying the nucleoprotein (NP) of CK/SD098 was avirulent in mice, with an MLD50 greater than 107.5 EID50. The NP proteins of these two viruses differ by two amino acids at positions 286 and 437. We further demonstrated that the two amino acid mutations A286V and T437M of NP independently slow down the process of NP import to and export from the nucleus, and thus jointly impaired the viral life cycle and attenuated the virulence of these H7N9 viruses in mice. Our study identified new virulence determinants in NP and provided novel targets for the development of live attenuated vaccine and antiviral drugs against influenza viruses.

 

Importance

The H7N9 influenza viruses that emerged in China in 2013 have caused over 1,500 human infections, with a mortality of nearly 40%. The viruses were initially low pathogenic but became highly pathogenic in chickens at the beginning of 2017 and caused severe disease outbreaks in poultry. Several studies suggest that the highly pathogenic H7N9 viruses have increased virulence in mammals; however, the genetic basis of the virulence of H7N9 viruses in mammals is not fully understood. Here, we found that two amino acids, 286A and 437T, in NP are prerequisites for the virulence of H7N9 viruses in mice, and that the mutations A286V and T437M collectively eliminate the virulence of H7N9 viruses in mice. Our study further demonstrated that the virulence of influenza virus is polygenic trait, and the newly identified virulence-related residues in NP may provide new targets for attenuated influenza vaccine and antiviral drug development.

Copyright © 2019 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Avian Influenza; H7N9; Viral pathogenesis; Animal models.

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Characterization of #H7N9 #avian #influenza viruses isolated from #duck #meat products (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Oct 25. doi: 10.1111/tbed.13398. [Epub ahead of print]

Characterization of H7N9 avian influenza viruses isolated from duck meat products.

Wu L1, Mitake H1, Kiso M1, Ito M1, Iwatsuki-Hirimoto K1, Yamayoshi S1, Lopes TJS1,2, Feng H1, Sumiyoshi R3, Shibata A3, Osaka H3, Imai M1, Watanabe T1, Kawaoka Y1,2,4.

Author information: 1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA. 3 Exotic Disease Inspection Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Aichi, Japan. 4 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

 

Abstract

Avian influenza H7N9 viruses have caused five epidemic waves of human infections since the first human cases were reported in 2013. In 2016, the initial low pathogenic avian influenza (LPAI) H7N9 viruses became highly pathogenic, acquiring multi-basic amino acids at the hemagglutinin cleavage site. This highly pathogenic avian influenza (HPAI) H7N9 viruses have been detected in poultry and humans in China, causing concerns of a serious threat to global public health. In Japan, both HPAI and LPAI H7N9 viruses were isolated from duck meat products carried illegally and relinquished voluntarily at the border by passengers on flights from China to Japan between 2016 and 2017. Some of the LPAI and HPAI H7N9 viruses detected at the border in Japan were characterized previously in chickens and ducks; however, their pathogenicity and replicative ability in mammals remain unknown. In this study, we assessed the biological features of two HPAI H7N9 virus isolates [A/duck/Japan/AQ-HE29-22/2017 (HE29-22) and A/duck/Japan/AQ-HE29-52/2017 (HE29-52); both of these viruses were isolated from duck meat at the border)] and an LPAI H7N9 virus isolate [A/duck/Japan/AQ-HE28-3/2016 (HE28-3)] in mice and ferrets. In mice, HE29-52 was more pathogenic than HE29-22 and HE28-3. In ferrets, the two HPAI virus isolates replicated more efficiently in the lower respiratory tract of the animals than did the LPAI virus isolate. Our results indicate that HPAI H7N9 viruses with potential to cause severe diseases in mammals have been illegally introduced to Japan.

© 2019 Blackwell Verlag GmbH.

KEYWORDS: H7N9; Highly pathogenic avian influenza; pathogenicity in mammals

PMID: 31650680 DOI: 10.1111/tbed.13398

Keywords: Avian Influenza; H7N9; Food safety.

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#Avian #Influenza A Viruses among Occupationally Exposed #Populations, #China, 2014–2016 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 12—December 2019 / Research

Avian Influenza A Viruses among Occupationally Exposed Populations, China, 2014–2016

Chuansong Quan1, Qianli Wang1, Jie Zhang, Min Zhao, Qigang Dai, Ting Huang, Zewu Zhang, Shenghua Mao, Yifei Nie, Jun Liu, Yun Xie, Baorong Zhang, Yuhai Bi, Weifeng Shi, Peipei Liu, Dayan Wang, Luzhao Feng, Hongjie Yu, William J. Liu  , and George F. Gao

Author affiliations: Chinese Center for Disease Control and Prevention, Beijing, China (C. Quan, J. Zhang, P. Liu, D. Wang, L. Feng, W.J. Liu, G.F. Gao); Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China (C. Quan, W. Shi); Fudan University, Shanghai, China (Q. Wang, H. Yu); Chinese Academy of Sciences, Beijing (M. Zhao, Y. Bi, G.F. Gao); Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China (Q. Dai); Sichuan Provincial Center for Disease Prevention and Control, Chengdu, China (T. Huang); Dongguan Municipal Center for Disease Control and Prevention, Dongguan, China (Z. Zhang); Shanghai Municipal Center for Disease Control and Prevention, Shanghai (S. Mao); Henan Provincial Center for Disease Control and Prevention, Zhengzhou, China (Y. Nie); Zaozhuang Center for Disease Control and Prevention, Zaozhuang, China (J. Liu); Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, China (Y. Xie); Aviation General Hospital, Beijing (B. Zhang)

 

Abstract

To determine the seroprevalence and seroconversion of avian influenza virus (AIV) antibodies in poultry workers, we conducted a seroepidemiologic study in 7 areas of China during December 2014–April 2016. We used viral isolation and reverse transcription PCR to detect AIVs in specimens from live poultry markets. We analyzed 2,124 serum samples obtained from 1,407 poultry workers by using hemagglutination inhibition and microneutralization assays. We noted seroprevalence of AIV antibodies for subtypes H9N2, H7N9, H6N1, H5N1-SC29, H5N6, H5N1-SH199, and H6N6. In serum from participants with longitudinal samples, we noted seroconversion, with >4-fold rise in titers, for H9N2, H7N9, H6N1, H5N1-SC29, H6N6, H5N6, and H5N1-SH199 subtypes. We found no evidence of H10N8 subtype. The distribution of AIV antibodies provided evidence of asymptomatic infection. We correlated AIV antibody prevalence in live poultry markets with increased risk for H7N9 and H9N2 infection among poultry workers.

Keywords: Avian Influenza; Human; China; Serology; Seroprevalence; H5N1; H5N6; H6N1; H6N6; H7N9; H9N2; Live poultry Markets.

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The #PB2 and M #genes are critical for the superiority of genotype S #H9N2 virus to genotype H in optimizing viral fitness of #H5Nx and #H7N9 #avian #influenza viruses in mice (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Oct 21. doi: 10.1111/tbed.13395. [Epub ahead of print]

The PB2 and M genes are critical for the superiority of genotype S H9N2 virus to genotype H in optimizing viral fitness of H5Nx and H7N9 avian influenza viruses in mice.

Hao X1,2,3, Hu J1,2,3, Wang X1,2,3, Gu M1,2,3, Wang J1,2,3, Liu D1,2,3, Gao Z1,2,3, Chen Y1,2,3, Gao R1,2,3, Li X1,2,3, Hu Z1,2,3, Hu S1,2,3, Liu X1,2,3, Peng D1,2,3, Jiao X2,3,4, Liu X1,2,3,4.

Author information: 1 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China. 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China. 3 Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China. 4 Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China.

 

Abstract

Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, and contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1-like M and PB2 genes for the earlier F/98-like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1-like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared to the F/98-like counterpart, while the G1-like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1-like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses.

© 2019 Blackwell Verlag GmbH.

KEYWORDS: G1-like M and PB2; H5Nx; H7N9; avian influenza virus; viral fitness

PMID: 31631569 DOI: 10.1111/tbed.13395

Keywords: Avian Influenza; H5N1; H7N9; H10N8; H9N2; Reassortant strains.

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