Characterization of viral #genomic #mutations in novel #influenza A (#H7N9)-infected #patients: the association between #oseltamivir-resistant variants and viral shedding duration (Virus Genes., abstract)

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

Virus Genes. 2019 Jul 13. doi: 10.1007/s11262-019-01678-8. [Epub ahead of print]

Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration.

Chen R1, Zou Q2,3, Xie G2,3, Yu F2,3, Yang X2,3, Cao L1, Huo Z4, Zheng S5,6.

Author information: 1 Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China. 2 Center of Clinical Laboratory, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China. 3 Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China. 4 Experimental Teaching Center, School of Basic Medical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China. zxhuo@zju.edu.cn. 5 Center of Clinical Laboratory, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China. zsfzheng@zju.edu.cn. 6 Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China. zsfzheng@zju.edu.cn.

 

Abstract

Since February 2013, human infections with the novel influenza A H7N9 virus have occurred in eastern China. It is important to detect mutations in viral genes and analyze the clinical features of patients and viral shedding duration related to neuraminidase inhibitor (NAI) resistance. We collected clinical specimens from 31 hospitalized H7N9 patients and sequenced NA, PB2, HA, and M gene fragments. Of the 31 identified patients, 7 (22.6%) carried the R292K substitution in NA, 30 (96.8%), 3 (9.7%), and 5 (16.1%) carried E627K, Q591K, and D701N mutations in PB2, respectively, and 2 (6.5%) carried both E627K and D701N mutations in PB2. All 26 identified patients harbored Q226L mutations and possessed only a single arginine (R) at cleavage sites in the HA and a S31N mutation in M2. Among 7 NA-R292K mutated patients, 3 died and 4 were discharged. There was no significant difference in the days that patients started oseltamivir treatment after symptom onset between NA-R292K mutant and NA-R292 wild-type patients (median days, 7 vs 6, P = 0.374). NA-R292K mutant patients had a significantly longer duration of viral shedding than NA-R292 wild-type patients after oseltamivir treatment (median days, 10 vs 5, P = 0.022). The mutation of R292K in NA conferring the potential ability of oseltamivir resistance resulted in prolonged viral duration and poor outcome and should be taken into consideration in the clinical management of infected patients.

KEYWORDS: Influenza A (H7N9); Mutation; Neuraminidase (NA); Oseltamivir resistance; Viral duration

PMID: 31302878 DOI: 10.1007/s11262-019-01678-8

Keywords: Avian Influenza; H7N9; Antivirals; Drugs Resistance; Oseltamivir; China; Human.

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Emergence of #Influenza A(#H7N4) Virus, #Cambodia (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 10—October 2019 / Research Letter

Emergence of Influenza A(H7N4) Virus, Cambodia

Dhanasekaran Vijaykrishna, Yi-Mo Deng, Miguel L. Grau, Matthew Kay, Annika Suttie, Paul F. Horwood, Wantanee Kalpravidh, Filip Claes, Kristina Osbjer, Phillipe Dussart, Ian G. Barr, and Erik A. Karlsson

Author affiliations: Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia (D. Vijaykrishna, Y.-M. Deng, M. Kay, I.G. Barr); Monash University, Melbourne (D. Vijaykrishna, M.L. Grau); Institut Pasteur du Cambodge, Phnom Penh, Cambodia (A. Suttie, P.F. Horwood, P. Dussart, E.A. Karlsson); James Cook University, Townsville, Queensland, Australia (P.F. Horwood); Food and Agriculture Organization of the United Nations, Bangkok, Thailand (W. Kalpravidh, F. Claes); Food and Agriculture Organization of the United Nations, Phnom Penh, Cambodia (K. Osbjer)

 

Abstract

Active surveillance in high-risk sites in Cambodia has identified multiple low-pathogenicity influenza A(H7) viruses, mainly in ducks. None fall within the A/Anhui/1/2013(H7N9) lineage; however, some A(H7) viruses from 2018 show temporal and phylogenetic similarity to the H7N4 virus that caused a nonfatal infection in Jiangsu Province, China, in December 2017.

Keywords: Avian Influenza; H7N4; Reassortant strain; Cambodia.

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A cross-reactive #human #monoclonal #antibody targets the conserved #H7 #antigenic site a from fifth wave #H7N9-infected humans (Antiviral Res., abstract)

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

Antiviral Res. 2019 Jul 9:104556. doi: 10.1016/j.antiviral.2019.104556. [Epub ahead of print]

A cross-reactive human monoclonal antibody targets the conserved H7 antigenic site a from fifth wave H7N9-infected humans.

Li M1, Chen L1, Wang Q1, Hao M2, Zhang X1, Liu L3, Yu X3, Yang C1, Xu J4, Chen J5, Gong R6.

Author information: 1 CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China; University of Chinese Academy of Sciences, Beijing, 100049, China. 2 CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China; National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. 3 Hubei Provincial Center for Disease Control and Prevention, Wuhan, 430079, China. 4 Hubei Provincial Center for Disease Control and Prevention, Wuhan, 430079, China. Electronic address: 609564945@qq.com. 5 CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China; National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. Electronic address: chenjj@wh.iov.cn. 6 CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China. Electronic address: gongr@wh.iov.cn.

 

Abstract

Subtype H7 avian influenza viruses have been found to be associated with human infection and represent a risk for global public health. In 2013, the emergence of H7N9 virus in human beings and persistent human infection in China raised the most serious pandemic threat. Here we identified a human monoclonal antibody, P52E03, targeting the hemagglutinin (HA) of subtype H7 influenza viruses (H7 antigen), from a convalescent patient infected with H7N9 in 2017. P52E03 showed in vitro hemagglutination inhibiting (HI) and neutralizing activity against subtype H7 viruses belonging to both North American and Eurasian lineages. Moreover, it could prophylactically protect mice against weight loss and death caused by challenge with lethal H7N9 viruses in vivo and, therefore, is a candidate for development of antiviral agent against H7N9 infection. By generating escape mutant variants, we found that a single G151E substitution in the viral H7 antigenic site A could abort the neutralizing activity. Computational structural prediction of the P52E03/H7 complex revealed that residues including G151 in and around the conserved antigenic A region are important for antigen recognition by the H7 cross-reactive antibody. Finally, we found that the P52E03 germline precursor (gHgL) antibody recognizes HA with measurable affinity, suggesting that its epitope is vulnerable to the human immune system and might elicit neutralizing antibodies (nAbs) in vivo after vaccination.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: Antibody; Epitope; H7N9; Hemagglutination inhibiting; Influenza virus; Neutralizing

PMID: 31299269 DOI: 10.1016/j.antiviral.2019.104556

Keywords: Avian Influenza; H7N9; Monoclonal antibodies.

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A novel #H7N3 #reassortant originating from the zoonotic #H7N9 highly pathogenic #avian #influenza viruses that has adapted to #ducks (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Jul 11. doi: 10.1111/tbed.13291. [Epub ahead of print]

A novel H7N3 reassortant originating from the zoonotic H7N9 highly pathogenic avian influenza viruses that has adapted to ducks.

Nakayama M1, Uchida Y1, Shibata A2, Kobayashi Y3, Mine J1, Takemae N1, Tsunekuni R1, Tanikawa T1, Harada R2, Osaka H2, Saito T1,4.

Author information: 1 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan. 2 Exotic Disease Inspection Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Tokoname, Aichi, 479-0881, Japan. 3 Pathological and Physiochemical Examination Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Yokohama, Kanagawa, 235-0008, Japan. 4 United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.

 

Abstract

The first human case of zoonotic H7N9 avian influenza virus (AIV) infection was reported in March 2013 in China. This virus continues to circulate in poultry in China while mutating to highly pathogenic AIVs (HPAIVs). Through monitoring at airports in Japan, a novel H7N3 reassortant of the zoonotic H7N9 HPAIVs, A/duck/Japan/AQ-HE30-1/2018 (HE30-1), was detected in a poultry meat product illegally brought by a passenger from China into Japan. We analyzed the genetic, pathogenic, and antigenic characteristics of HE30-1 by comparing it with previous zoonotic H7N9 AIVs and their reassortants. Phylogenetic analysis of the entire HE30-1 genomic sequence revealed that it comprised at least three different sources; the HA (H7), PB1, PA, NP, M, and NS segments of HE30-1 were directly derived from H7N9 AIVs, whereas the NA (N3) and PB2 segments of HE30-1 were unrelated to zoonotic H7N9. Experimental infection revealed that HE30-1 was lethal in chickens but not in domestic or mallard ducks. HE30-1 was shed from and replicated in domestic and mallard ducks and chickens, whereas previous zoonotic H7N9 AIVs have not adapted well to ducks. This finding suggests the possibility that HE30-1 may disseminate to remote area by wild bird migration once it establishes in wild bird population. A hemagglutination-inhibition assay indicated that antigenic drift has occurred among the reassortants of zoonotic H7N9 AIVs; HE30-1 showed similar antigenicity to some of those H7N9 AIVs, suggesting it might be prevented by the H5/H7 inactivated vaccine that was introduced in China in 2017. Our study reports the emergence of a new reassortant of zoonotic H7N9 AIVs with novel viral characteristics and warns of the challenge we still face to control the zoonotic H7N9 AIVs and their reassortants.

This article is protected by copyright. All rights reserved.

KEYWORDS: adaptation to ducks; animal experiments; novel H7N3 reassortant; zoonotic H7N9 avian influenza viruses

PMID: 31293102 DOI: 10.1111/tbed.13291

Keywords: Avian Influenza; H7N3; H7N9; Reassortant strain; Animal models.

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Serial Section Array Scanning Electron Microscopy Analysis of Cells from #Lung #Autopsy #Specimens Following #Fatal A/ #H1N1pdm09 #Influenza Virus #Infection (J Virol., abstract)

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

Serial Section Array Scanning Electron Microscopy Analysis of Cells from Lung Autopsy Specimens Following Fatal A/H1N1 2009 Pandemic Influenza Virus Infection

Michiyo Kataoka, Kinji Ishida, Katsutoshi Ogasawara, Takayuki Nozaki, Yoh-ichi Satoh, Tetsutaro Sata, Yuko Sato, Hideki Hasegawa, Noriko Nakajima

DOI: 10.1128/JVI.00644-19

 

ABSTRACT

A/H1N1 2009 pandemic influenza virus (A/H1N1/pdm09) was first identified as a novel pandemic influenza A virus (IAV) in 2009. Previously, we reported that many viral antigens were detected in type II alveolar epithelial cells (AEC-IIs) within autopsied lung tissue from a patient with A/H1N1/pdm09 pneumonia. It is important to identify the association between the virus and host cells to elucidate the pathogenesis of IAV pneumonia. To investigate the distribution of virus particles and morphological changes in host cells, the autopsied lung specimens from this patient were examined using transmission electron microscopy (TEM) and a novel scanning electron microscopy (SEM) method. We focused on AEC-IIs as viral antigen-positive cells, and on monocytes/macrophages (Ms/MΦs) and neutrophils (Neus) as innate immune cells. We identified virus particles and intranuclear dense tubules, which are associated with matrix 1 (M1) proteins from IAV. Large-scale two-dimensional observation was enabled by digitally ‘stitching’ together contiguous SEM images. A single whole cell analysis using a serial section array (SSA)-SEM identified virus particles in vesicles within the cytoplasm and/or around the cell surface of AEC-IIs, Ms/MΦs, and Neus; however, intranuclear dense tubules were found only in AEC-IIs. Computer-assisted processing of SSA-SEM images from each cell type enabled 3D modeling of the distribution of virus particles within an ACE-II, a M/MΦ, and a Neu.

 

IMPORTANCE

Generally, it is difficult to observe IAV particles in post-mortem samples from patients with seasonal influenza. In fact, only a few viral antigens are detected in bronchial epithelial cells from autopsied lung sections. Previously, we detected many viral antigens in AEC-IIs from the lung. This was because the majority of A/H1N1/pdm09 in the lung tissue harbored an aspartic acid to glycine substitution at position 222 (D222G) of the hemagglutinin protein. A/H1N1/pdm09 harboring the D222G substitution has a receptor-binding preference for α-2,3-linked sialic acids expressed on human AECs and infects them in the same way as H5N1 and H7N9 avian IAVs. Here, we report the first successful observation of virus particles not only in AEC-IIs, but also in Ms/MΦs and Neus, using electron microscopy. The finding of a M/MΦ harboring numerous virus particles within vesicles and at the cell surface suggests that Ms/MΦs are involved in the pathogenesis of IAV primary pneumonia.

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

Keywords: Influenza A; Seasonal Influenza; Pandemic Influenza; Avian Influenza; H1N1pdm09; H5N1; H7N9; Viral pathogenesis.

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Susceptibility of #Influenza A, B, C, and D Viruses to #Baloxavir (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 10—October 2019 / Dispatch

Susceptibility of Influenza A, B, C, and D Viruses to Baloxavir

Vasiliy P. Mishin, Mira C. Patel, Anton Chesnokov, Juan De La Cruz, Ha T. Nguyen, Lori Lollis, Erin Hodges, Yunho Jang, John Barnes, Timothy Uyeki, Charles T. Davis, David E. Wentworth, and Larisa V. Gubareva

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (V.P. Mishin, M.C. Patel, A. Chesnokov, J. De La Cruz, H.T. Nguyen, L. Lollis, E. Hodges, Y. Jang, J. Barnes, T. Uyeki, C.T. Davis, D.E. Wentworth, L.V. Gubareva); Battelle Memorial Institute, Atlanta (M.C. Patel, J. De La Cruz, H.T. Nguyen, L. Lollis)

 

Abstract

Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types of influenza viruses (90% effective concentration range 1.2–98.3 nmol/L); susceptibility pattern was influenza A ˃ B ˃ C ˃ D. This drug also inhibited influenza A viruses of avian and swine origin, including viruses that have pandemic potential and those resistant to neuraminidase inhibitors.

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Favipiravir; Baloxavir; Influenza A; Influenza B; Influenza C; Influenza D; H1N1pdm09; H3N2; H7N9.

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A Novel #Antigenic #Drift of #Avian #Influenza A(#H7N9) Virus in #Poultry, #China, 2018 (J Infect Dis., abstract)

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

A Novel Antigenic Drift of Avian Influenza A(H7N9) Virus in Poultry, China, 2018

Weixin Jia, Xiaohui Wen, Shumin Xie, Yixue Dai, Zhixian Li, Xiao Wang, Jingkai Hu, Xuanjiang Jin, Xiao Li, Wenbao Qi, Abani K Pradhan, Ming Liao

The Journal of Infectious Diseases, jiz190, https://doi.org/10.1093/infdis/jiz190

Published: 08 July 2019

Issue Section: Correspondence

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TO THE EDITOR — In their recent article, Ning et al [1] analyzed antigenic drift of influenza A(H7N9) virus haemagglutinin (HA). Their findings showed that some key mutations affecting antigenicity may have appeared in H7N9 in the past 5 years. To further evaluate the changes of antigenicity of H7N9, we studied the antigenicity and molecular characteristics of a new H7N9 virus isolated from poultry. We found a novel antigenic drift, which is different from previous findings. To our knowledge, this is the first antigenic change found after the implementation of China’s immunization policy in poultry.

After the emergence of the highly pathogenic H7N9 subtype influenza…

(…)

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This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Avian Influenza; H7N9; Vaccines; Poultry.

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