Specificity, #Kinetics and Longevity of #Antibody #Responses to #Avian #Influenza A(#H7N9) Virus #Infection in #Humans (J Infect., abstract)

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

J Infect. 2020 Jan 16. pii: S0163-4453(20)30025-6. doi: 10.1016/j.jinf.2019.11.024. [Epub ahead of print]

Specificity, Kinetics and Longevity of Antibody Responses to Avian Influenza A(H7N9) Virus Infection in Humans.

Chen J1, Zhu H2, Horby PW3, Wang Q1, Zhou J1, Jiang H4, Liu L5, Zhang T6, Zhang Y7, Chen X1, Deng X1, Nikolay B8, Wang W1, Cauchemez S8, Guan Y2, Uyeki TM9, Yu H10.

Author information: 1 School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, 200032, China. 2 Joint Institute of Virology (STU-HKU), Shantou University, Shantou, 515041, China; State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong SAR, China. 3 Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK. 4 Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China. 5 Joint Institute of Virology (STU-HKU), Shantou University, Shantou, 515041, China. 6 Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330000, China. 7 Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China. 8 Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, 75015 Paris, France. 9 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 10 School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, 200032, China. Electronic address: yhj@fudan.edu.cn.




The long-term dynamics of antibody responses in patients with influenza A(H7N9) virus infection are not well understood.


We conducted a longitudinal serological follow-up study in patients who were hospitalized with A(H7N9) virus infection, during 2013-2018. A(H7N9) virus-specific antibody responses were assessed by hemagglutination inhibition (HAI) and neutralization (NT) assays. A random intercept model was used to fit a curve to HAI antibody responses over time. HAI antibody responses were compared by clinical severity.


Of 67 patients with A(H7N9) virus infection, HAI antibody titers reached 40 on average 11 days after illness onset and peaked at a titer of 290 after three months, and average titers of ≥80 and ≥40 were present until 11 months and 22 months respectively. HAI antibody responses were significantly higher in patients who experienced severe disease, including respiratory failure and acute respiratory distress syndrome, compared with patients who experienced less severe illness.


Patients with A(H7N9) virus infection who survived severe disease mounted higher antibody responses that persisted for longer periods compared with those that experienced moderate disease. Studies of convalescent plasma treatment for A(H7N9) patients should consider collection of donor plasma from survivors of severe disease between 1-11 months after illness onset.

Copyright © 2020 Elsevier Ltd. All rights reserved.

KEYWORDS: Antibody response; Clinical severity; Follow-up; Influenza A(H7N9)

PMID: 31954742 DOI: 10.1016/j.jinf.2019.11.024

Keywords: Avian Influenza; H7N9; Serotherapy; Human.


#H7N9 #Influenza Virus Containing a #Polybasic HA Cleavage Site Requires Minimal Host #Adaptation to Obtain a Highly Pathogenic Disease Phenotype in Mice (Viruses, abstract)

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

Viruses. 2020 Jan 5;12(1). pii: E65. doi: 10.3390/v12010065.

H7N9 Influenza Virus Containing a Polybasic HA Cleavage Site Requires Minimal Host Adaptation to Obtain a Highly Pathogenic Disease Phenotype in Mice.

Chan M1, Leung A1, Hisanaga T2, Pickering B2,3, Griffin BD1,3, Vendramelli R1, Tailor N1, Wong G4,5, Bi Y6, Babiuk S2, Berhane Y2, Kobasa D1,3.

Author information: 1 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB R3E 3R2, Canada. 2 National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB R3E 3M4, Canada. 3 Department of Medical Microbiology and Infectious Diseases, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada. 4 Institut Pasteur of Shanghai, Chinese Academy of Sciences, Life Science Research Building 320 Yueyang Road, Xuhui District, Shanghai 200031, China. 5 Département de microbiologie-infectiologie et d’immunologie, Université Laval, 1050 avenue de la Médecine, QC G1V 0A6, Canada. 6 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.



Low pathogenic avian influenza (LPAI) H7N9 viruses have recently evolved to gain a polybasic cleavage site in the hemagglutinin (HA) protein, resulting in variants with increased lethality in poultry that meet the criteria for highly pathogenic avian influenza (HPAI) viruses. Both LPAI and HPAI variants can cause severe disease in humans (case fatality rate of ~40%). Here, we investigated the virulence of HPAI H7N9 viruses containing a polybasic HA cleavage site (H7N9-PBC) in mice. Inoculation of mice with H7N9-PBC did not result in observable disease; however, mice inoculated with a mouse-adapted version of this virus, generated by a single passage in mice, caused uniformly lethal disease. In addition to the PBC site, we identified three other mutations that are important for host-adaptation and virulence in mice: HA (A452T), PA (D347G), and PB2 (M483K). Using reverse genetics, we confirmed that the HA mutation was the most critical for increased virulence in mice. Our study identifies additional disease determinants in a mammalian model for HPAI H7N9 virus. Furthermore, the ease displayed by the virus to adapt to a new host highlights the potential for H7N9-PBC viruses to rapidly acquire mutations that may enhance their risk to humans or other animal species.

KEYWORDS: H7N9; HPAI; influenza virus; mammalian adaptation; mice; polybasic HA

PMID: 31948040 DOI: 10.3390/v12010065

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


Association Between #Cardiac #Injury and #Mortality in Hospitalized Patients Infected With #Avian #Influenza A (#H7N9) Virus (Crit Care Med., abstract)

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

Crit Care Med. 2020 Jan 9. doi: 10.1097/CCM.0000000000004207. [Epub ahead of print]

Association Between Cardiac Injury and Mortality in Hospitalized Patients Infected With Avian Influenza A (H7N9) Virus.

Gao C1,2, Wang Y3, Gu X4,5, Shen X6, Zhou D7, Zhou S8, Huang JA9, Cao B3,5,10, Guo Q2; for the Community-Acquired Pneumonia–China Network.

Author information: 1 Department of Critical Care Medicine, Dushuhu Public Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China. 2 Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. 3 Department of Pulmonary and Critical Care Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Capital Medical University, Beijing, China. 4 Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China. 5 Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China. 6 Department of Critical Care Medicine, The Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, China. 7 Department of infectious diseases, Taizhou People’s Hospital, Taizhou, Jiangsu, China. 8 Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, China. 9 Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. 10 Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.




To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus.


Retrospective cohort study.


A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus-infected patients between January 22, 2015, and June 16, 2017.


A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis.




Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower PaO2/FIO2 (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31-3.24) during hospitalization.


Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.

PMID: 31923027 DOI: 10.1097/CCM.0000000000004207

Keywords: Avian Influenza; H7N9; Human; Cardiology.


Comparative #Pathogenicity and #Transmissibility of #H1N1pdm09, #Avian #H5N1, and #Human #H7N9 #Influenza Viruses in Tree #Shrews (Front Microbiol., abstract)

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

Front Microbiol. 2019 Dec 20;10:2955. doi: 10.3389/fmicb.2019.02955. eCollection 2019.

Comparative Pathogenicity and Transmissibility of Pandemic H1N1, Avian H5N1, and Human H7N9 Influenza Viruses in Tree Shrews.

Xu S1, Li X1, Yang J1, Wang Z1, Jia Y1, Han L1, Wang L1, Zhu Q1.

Author information: 1 State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.



Influenza A viruses (IAVs) continuously challenge the poultry industry and human health. Studies of IAVs are still hampered by the availability of suitable animal models. Chinese tree shrews (Tupaia belangeri chinensis) are closely related to primates physiologically and genetically, which make them a potential animal model for human diseases. In this study, we comprehensively evaluated infectivity and transmissibility in Chinese tree shrews by using pandemic H1N1 (A/Sichuan/1/2009, pdmH1N1), avian-origin H5N1 (A/Chicken/Gansu/2/2012, H5N1) and early human-origin H7N9 (A/Suzhou/SZ19/2014, H7N9) IAVs. We found that these viruses replicated efficiently in primary tree shrew cells and tree shrews without prior adaption. Pathological lesions in the lungs of the infected tree shrews were severe on day 3 post-inoculation, although clinic symptoms were self-limiting. The pdmH1N1 and H7N9 viruses, but not the H5N1 virus, transmitted among tree shrews by direct contact. Interestingly, we also observed that unadapted H7N9 virus could transmit from tree shrews to naïve guinea pigs. Virus-inoculated tree shrews generated a strong humoral immune response and were protected from challenge with homologous virus. Taken together, our findings suggest the Chinese tree shrew would be a useful mammalian model to study the pathogenesis and transmission of IAVs.

Copyright © 2019 Xu, Li, Yang, Wang, Jia, Han, Wang and Zhu.

KEYWORDS: H1N1; H5N1; H7N9; infectivity; transmissibility; tree shrew

PMID: 31921093 PMCID: PMC6933948 DOI: 10.3389/fmicb.2019.02955

Keywords: Influenza A; H7N9; H5N1; H1N1pdm09; Animal models.


The fit of #codon usage of #human-isolated #avian #influenza A viruses to human (Infect Genet Evol., abstract)

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

Infect Genet Evol. 2020 Jan 6:104181. doi: 10.1016/j.meegid.2020.104181. [Epub ahead of print]

The fit of codon usage of human-isolated avian influenza A viruses to human.

Luo W1, Tian L2, Gan Y1, Chen E1, Shen X1, Pan J1, Irwin DM3, Chen RA4, Shen Y5.

Author information: 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. 2 Guangdong Provincial Hospital of Chinese Medicine, Zhuhai 519015, China. 3 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada; Banting and Best Diabetes Centre, University of Toronto, Toronto M5S 1A8, Canada. 4 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Zhaoqing Institute of Biotechnology, Zhaoqing 526238, China. Electronic address: chensa727@126.com. 5 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Zhaoqing Institute of Biotechnology, Zhaoqing 526238, China. Electronic address: shenyy@scau.edu.cn.



Avian influenza A viruses (AIVs) classify into 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes. Even though H1N1 and H3N2 subtypes usually circulate among humans leading to infection, occasionally, H5, H6, H7, H9, and H10 that circulate in poultry also infect humans, and especially H5N1 and H7N9. Efficient virus replication is a critical factor that influences infection. Codon usage of a virus must coevolve with its host for efficient viral replication, therefore, we conduct a comprehensive analysis of codon usage bias in human-isolated AIVs to test their adaptation to host expression system. The relative synonymous codon usage (RSCU) pattern, and the codon adaptation index (CAI) are calculated for this purpose. We find that all human-isolated AIVs tend to eliminate GC and CpG compositions, which may prevent activation of the host innate immune system. Although codon usage differs between AIV subtypes, our data support the conclusion that natural selection has played a major role and mutation pressure a minor role in shaping codon usage bias in all AIVs. Our efforts discover that codon usage of genes encoding surface proteins of H5N1, and the polymerase genes of H7N9 has better fit to the human expression system. This may associate with their better replication and infection in human.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: Adaptation; Avian influenza A viruses; Codon usage; H5N1; H7N9

PMID: 31918040 DOI: 10.1016/j.meegid.2020.104181

Keywords: Avian Influenza; H5N1; H7N9; Human; Evolution.


Distribution of #Avian #Influenza A Viruses in #Poultry-Related #Environment and Its Association with #Human #Infection in #Henan, 2016 to 2017 (Biomed Environ Sci., abstract)

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

Biomed Environ Sci. 2019 Nov;32(11):797-803. doi: 10.3967/bes2019.101.

Distribution of Avian Influenza A Viruses in Poultry-Related Environment and Its Association with Human Infection in Henan, 2016 to 2017.

Ma HX1, Wang RL2, Nie YF2, Su J2, Li DX1, Li Y1, DU YH1, Wei HY1, Li XL1, Wang Z2, Xu BL1, Huang XY1.

Author information: 1 Henan Centers for Disease Control and Prevention, Zhengzhou 450016, Henan, China; Key Laboratory of Pathogenic Microorganisms of Henan Province, Zhengzhou 450016, Henan, China. 2 Henan Centers for Disease Control and Prevention, Zhengzhou 450016, Henan, China.




To survey avian influenza A viruses (AIVs) in the environment and explore the reasons for the surge in human H7N9 cases.


A total of 1,045 samples were collected from routine surveillance on poultry-related environments and 307 samples from human H7N9 cases-exposed environments in Henan from 2016 to 2017. The nucleic acids of influenza A (Flu A), H5, H7, and H9 subtypes were detected by real-time polymerase chain reaction.


A total of 27 H7N9 cases were confirmed in Henan from 2016 to 2017, 24 had a history of live poultry exposure, and 15 had H7N9 virus detected in the related live poultry markets (LPMs). About 96% (264/275) Flu A positive-environmental samples were from LPMs. H9 was the main AIV subtype (10.05%) from routine surveillance sites with only 1 H7-positive sample, whereas 21.17% samples were H7-positive in H7N9 cases-exposed environments. Samples from H7N9 cases-exposed LPMs (47.56%) had much higher AIVs positive rates than those from routine surveillance sites (12.34%). The H7+H9 combination of mixed infection was 78.18% (43/55) of H7-positive samples and 41.34% (43/104) of H9-positive samples.


The contamination status of AIVs in poultry-related environments is closely associated with the incidence of human infection caused by AIVs. Therefore, systematic surveillance of AIVs in LPMs in China is essential for the detection of novel reassortant viruses and their potential for interspecies transmission.

Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

KEYWORDS: Avian influenza virus; Exposure environments; Human H7N9 cases; Live poultry market; Routine surveillance

PMID: 31910937 DOI: 10.3967/bes2019.101

Keywords: Avian Influenza; H7N9; H9N2; Poultry; Human; China; Henan.


Protective efficacy of anti-neuraminidase #monoclonal #antibodies against #H7N9 #influenza virus #infection (Emerg Microbes Infect., abstract)

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

Emerg Microbes Infect. 2020 Dec;9(1):78-87. doi: 10.1080/22221751.2019.1708214.

Protective efficacy of anti-neuraminidase monoclonal antibodies against H7N9 influenza virus infection.

Xiong FF1, Liu XY1, Gao FX1,2, Luo J1, Duan P1, Tan WS2, Chen Z1.

Author information: 1 Shanghai Institute of Biological Products, Shanghai, People’s Republic of China. 2 East China University of Science and Technology, Shanghai, People’s Republic of China.



The H7N9 influenza virus has been circulating in China for more than six years. The neuraminidase (NA) has gained great concern for the development of antiviral drugs, therapeutic antibodies, and new vaccines. In this study, we screened seven mouse monoclonal antibodies (mAbs) and compared their protective effects against H7N9 influenza virus. The epitope mapping from escape mutants showed that all the seven mAbs could bind to the head region of the N9 NA close to the enzyme activity sites, and four key sites of N9 NA were reported for the first time. The mAbs D3 and 7H2 could simultaneously inhibit the cleavage of the sialic acid of fetuin protein with large molecular weight and NA-XTD with small molecule weight in the NA inhibition experiment, prevent the formation of virus plaque at a low concentration, and effectively protect the mice from the challenge of the lethal dose of H7N9 virus.

KEYWORDS: H7N9 influenza virus; NA epitope; monoclonal antibodies; neuraminidase; protection

PMID: 31894728 DOI: 10.1080/22221751.2019.1708214

Keywords: Avian Influenza; H7N9; Monoclonal antibodies; Animal models.