#Comparison of #Pathological Changes and #Pathogenic Mechanisms Caused by #H1N1 Influenza Virus, HPAI #H5N1, #SARS-CoV, #MERS-CoV and 2019-nCoV #Coronavirus (Zhonghua Bing Li Xue Za Zhi, abstract)

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

Zhonghua Bing Li Xue Za Zhi, 40 (0), E006 2020 Mar 16 [Online ahead of print]

[Comparison of Pathological Changes and Pathogenic Mechanisms Caused by H1N1 Influenza Virus, Highly Pathogenic H5N1 Avian Influenza Virus, SARS-CoV, MERS-CoV and 2019-nCoV Coronavirus]

[Article in Chinese]

M Liu 1, R E Feng 2, Q Li 3, H K Zhang 1, Y G Wang 1

Affiliations: 1 Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China. 2 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. 3 Shunyi Hospital of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 101300, China.

PMID: 32174094 DOI: 10.3760/cma.j.cn112151-20200301-00155



The rapid development of the new coronavirus pneumonia epidemic in Wuhan, China, has caused severe impact on the country, but so far, little is known about the pathological changes and pathogenesis of the new coronavirus pneumonia. This article summarizes the pathological changes of severe influenza virus H1N1, highly pathogenic avian influenza virus H5N1, SARS-CoV, MERS-CoV, and 2019-nCoV coronavirus that cause major outbreaks of viral infectious diseases. The autopsy lung tissues are diffuse. Alveolar damage (DAD), but pathological manifestations caused by different viruses are different. Severe influenza virus 2009 H1N1 virus binds to receptors α-2,6-SA and α-2,3-SA, except for DAD lesions It is often accompanied by inflammatory lesions of the upper respiratory tract, trachea, bronchi and bronchioles, and is more likely to be complicated by bacterial infection. The highly pathogenic avian influenza virus H5N1 mainly binds α-2,3-SA receptors, mainly involving alveolar epithelium and bronchioles. Rarely, upper respiratory tract and trachea and bronchial lesions are often associated with focal pulmonary hemorrhage and lung tissue necrosis. Mechanization and fibrosis are rare. SARS-CoV enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and the lesions are related to the course of disease. The DAD exudation period is generally seen in patients who die within 10 to 14 days. Patients with a disease course of more than 10 days showed mechanized DAD, often accompanied by occlusive bronchiolitis with organic pneumonia-like changes and significant multinucleated giant cells in the alveolar cavity. In patients with SARS-CoV and H5N1 infection, lymphocyte depletion in the spleen and lymph nodes, acute tubular necrosis, and hemophagocytic cells in the bone marrow were seen in the extrapulmonary organs.

Keywords: SARS-CoV-2; SARS-CoV; H1N1pdm09; H5N1.


#Avian #influenza #human #infections at the human-animal interface (J Infect Dis., abstract)

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

Avian influenza human infections at the human-animal interface

Damien A M Philippon, Peng Wu, Benjamin J Cowling, Eric H Y Lau

The Journal of Infectious Diseases, jiaa105, https://doi.org/10.1093/infdis/jiaa105

Published: 10 March 2020




Avian influenza A viruses (AIVs) are among the most concerning emerging and re-emerging pathogens because of the potential risk in causing an influenza pandemic with catastrophic impact. The recent increase in domestic animals and poultry worldwide was followed by an increase of human AIV outbreaks reported.


We reviewed the epidemiology of human infections with AIV from the literature including reports from the World Health Organization, extracting information on virus subtype, time, location, age, sex, outcome and exposure.


We described the characteristics of more than 2,500 laboratory-confirmed human infections with AIVs. Human infections with H5N1 and H7N9 were more frequently reported than other subtypes. The risk of death was highest among reported cases infected with H5N1, H5N6, H7N9 and H10N8 infections. Older people and males tended to have a lower risk of infection with most AIV subtypes, except for H7N9. Visiting live poultry markets were mostly reported by H7N9, H5N6 and H10N8 cases, while exposure to sick or dead bird mostly reported by H5N1, H7N2, H7N3, H7N4, H7N7 and H10N7 cases.


Understanding the profile of human cases of different AIV subtypes would guide control strategy. Continued monitoring of human infections with AIVs is essential for pandemic preparedness.

avian influenza, human infection, review

Issue Section:  Review

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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; Human; H5N1; H5N6; H7N3; H7N7; H7N9; H9N2; H10N8.


Quantifying within-host #diversity of #H5N1 #influenza viruses in #humans and #poultry in #Cambodia (PLOS Pathog., abstract)

[Source: PLOS Pathogens, full page: (LINK). Abstract, edited.]


Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia

Louise H. Moncla , Trevor Bedford, Philippe Dussart, Srey Viseth Horm, Sareth Rith, Philippe Buchy, Erik A. Karlsson, Lifeng Li, Yongmei Liu, Huachen Zhu, Yi Guan, Thomas C. Friedrich, Paul F. Horwood


Published: January 17, 2020 / DOI: https://doi.org/10.1371/journal.ppat.1008191 / This is an uncorrected proof.



Avian influenza viruses (AIVs) periodically cross species barriers and infect humans. The likelihood that an AIV will evolve mammalian transmissibility depends on acquiring and selecting mutations during spillover, but data from natural infection is limited. We analyze deep sequencing data from infected humans and domestic ducks in Cambodia to examine how H5N1 viruses evolve during spillover. Overall, viral populations in both species are predominated by low-frequency (<10%) variation shaped by purifying selection and genetic drift, and half of the variants detected within-host are never detected on the H5N1 virus phylogeny. However, we do detect a subset of mutations linked to human receptor binding and replication (PB2 E627K, HA A150V, and HA Q238L) that arose in multiple, independent humans. PB2 E627K and HA A150V were also enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adaptive. Our data show that H5N1 viruses generate putative human-adapting mutations during natural spillover infection, many of which are detected at >5% frequency within-host. However, short infection times, genetic drift, and purifying selection likely restrict their ability to evolve extensively during a single infection. Applying evolutionary methods to sequence data, we reveal a detailed view of H5N1 virus adaptive potential, and develop a foundation for studying host-adaptation in other zoonotic viruses.


Author summary

H5N1 avian influenza viruses can cross species barriers and cause severe disease in humans. H5N1 viruses currently cannot replicate and transmit efficiently among humans, but animal infection studies and modeling experiments have suggested that human adaptation may require only a few mutations. However, data from natural spillover infection has been limited, posing a challenge for risk assessment. Here, we analyze a unique dataset of deep sequence data from H5N1 virus-infected humans and domestic ducks in Cambodia. We find that well-known markers of human receptor binding and replication arise in multiple, independent humans. We also find that 3 mutations detected within-host are enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adapting. However, we also show that within-host evolution in both humans and ducks are shaped heavily by purifying selection and genetic drift, and that a large fraction of within-host variation is never detected on the H5N1 phylogeny. Taken together, our data show that H5N1 viruses do generate human-adapting mutations during natural infection. However, short infection times, purifying selection, and genetic drift may severely limit how much H5N1 viruses can evolve during the course of a single infection.


Citation: Moncla LH, Bedford T, Dussart P, Horm SV, Rith S, Buchy P, et al. (2020) Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia. PLoS Pathog 16(1): e1008191. https://doi.org/10.1371/journal.ppat.1008191

Editor: Wendy S. Barclay, Imperial College London, UNITED KINGDOM

Received: July 8, 2019; Accepted: November 4, 2019; Published: January 17, 2020

Copyright: © 2020 Moncla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All raw sequence data are available in the SRA under accession number PRJNA547644 (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA547644). All code used to analyze the data, as well as data files with within-host variant calls and phylogenetic trees are available at https://github.com/blab/h5n1-cambodia.

Funding: The study was funded by the US Agency for International Development (grant No. AID-442-G-14-00005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: Dr. Philippe Buchy is a former Head of Virology at Institut Pasteur du Cambodge and is currently an employee of GSK Vaccines, Singapore. The other authors declare no conflict of interest.

Keywords: Avian Influenza, H5N1, Human, Poultry, Cambodia.


Assessing the #susceptibility of highly pathogenic #avian #influenza #H5N1 viruses to #oseltamivir using embryonated chicken #eggs (Indian J Med Res., abstract)

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

Indian J Med Res. 2019 Nov;150(5):486-491. doi: 10.4103/ijmr.IJMR_845_18.

Assessing the susceptibility of highly pathogenic avian influenza H5N1 viruses to oseltamivir using embryonated chicken eggs.

Tare DS1, Kode SS1, Hurt AC2, Pawar SD3.

Author information: 1 Avian Influenza Group, ICMR-National Institute of Virology-Microbial Containment Complex, Pune, Maharashtra, India. 2 WHO Collaborating Centre for Reference & Research on Influenza (VIDRL), Peter Doherty Institute for Infection & Immunity, Melbourne VIC 3000, Australia. 3 ICMR-National Institute of Virology-Mumbai Unit, Mumbai, Maharashtra, India.




The susceptibility of influenza viruses to neuraminidase inhibitors (NAIs) is studied using enzyme-based assays, sequence analysis and in vitro and in vivo studies. Oseltamivir carboxylate (OC) is the active prodrug of the NAI oseltamivir. There is lack of information on the use of embryonated chicken eggs for studying susceptibility of highly pathogenic avian influenza (HPAI) H5N1 viruses to antiviral drugs. The aim of the present study was to assess the use of 10 day old embryonated chicken eggs for studying antiviral susceptibility of HPAI H5N1 viruses.


Two HPAI H5N1 viruses isolated from India were used in the study. Fluorescence-based NAI assay was performed to determine antiviral susceptibility of these viruses. In ovo antiviral assays were carried out using 10 day old embryonated chicken eggs. The virus dilutions were incubated with 14 μg/ml of OC and inoculated in the allantoic cavity. In the eggs, 50 per cent egg infectious dose (EID50) titres as well as mortality were quantitated.


The two viruses used were susceptible to OC in the NAI assay. It was found that there was a significant drop in EID50titres; however, no significant protection from mortality after OC treatment was observed.


By measuring viral titres, the egg model was suitable to study the susceptibility of HPAI viruses to antiviral drugs along with NAI assay. The present study highlights the use of eggs as a model to study susceptibility of HPAI viruses to OC.

KEYWORDS: Antivirals – embryonated chicken eggs – H5N1 – highly pathogenic avian influenza – oseltamivir

PMID: 31939392 DOI: 10.4103/ijmr.IJMR_845_18

Keywords: Antivirals; Drugs resistance; Avian Influenza; H5N1; Animal models.


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.


Evaluation of #potential #risk of #transmission of #avian #influenza A viruses at live #bird #markets in response to unusual #crow die-offs in #Bangladesh (Influenza Other Respir Viruses, abstract)

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

Influenza Other Respir Viruses. 2020 Jan 7. doi: 10.1111/irv.12716. [Epub ahead of print]

Evaluation of potential risk of transmission of avian influenza A viruses at live bird markets in response to unusual crow die-offs in Bangladesh.

Rahman M1,2, Mangtani P3, Uyeki TM4, Cardwell JM1, Torremorell M5, Islam A6, Samad MA7, Muraduzzaman AKM2, Giasuddin M7, Sarkar S2, Alamgir ASM2, Salimuzzaman M2, Flora MS2.

Author information: 1 Royal Veterinary College, Hatfield, UK. 2 Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh. 3 London School of Hygiene and Tropical Medicine, London, UK. 4 Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA. 5 University of Minnesota, Twin Cities, MN, USA. 6 EcoHealth Alliance, New York, NY, USA. 7 Bangladesh Livestock Research Institute (BLRI), Savar, Bangladesh.



In response to unusual crow die-offs from avian influenza A(H5N1) virus infection during January-February 2017 in Dhaka, Bangladesh, a One Health team assessed potential infection risks in live bird markets (LBMs). Evidence of aerosolized avian influenza A viruses was detected in LBMs and in the respiratory tracts of market workers, indicating exposure and potential for infection. This study highlighted the importance of surveillance platforms with a coordinated One Health strategy to investigate and mitigate zoonotic risk.

© 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

KEYWORDS: Bangladesh; avian influenza; avian influenza A virus; influenza in birds; live bird market; pathogen transmission

PMID: 31912608 DOI: 10.1111/irv.12716

Keywords: Avian Influenza; H5N1; Poultry; Live poultry markets; Bangladesh.