Avian Influenza Human Infections at the Human-Animal Interface

2020 ◽  
Vol 222 (4) ◽  
pp. 528-537 ◽  
Author(s):  
Damien A M Philippon ◽  
Peng Wu ◽  
Benjamin J Cowling ◽  
Eric H Y Lau
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Control Strategies ◽  
Influenza Pandemic ◽  
World Health ◽  
Emerging Pathogens ◽  
Influenza A Viruses ◽  
Dead Bird ◽  
Risk Of Death ◽  
Human Infections

Abstract Background Avian influenza A viruses (AIVs) are among the most concerning emerging and re-emerging pathogens because of the potential risk for 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. Methods 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. Results We described the characteristics of more than 2500 laboratory-confirmed human infections with AIVs. Human infections with H5N1 and H7N9 were more frequently reported than other subtypes. 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 was mostly reported by H7N9, H5N6, and H10N8 cases, while exposure to sick or dead bird was mostly reported by H5N1, H7N2, H7N3, H7N4, H7N7, and H10N7 cases. Conclusions Understanding the profile of human cases of different AIV subtypes would guide control strategies. Continued monitoring of human infections with AIVs is essential for pandemic preparedness.

scholarly journals Avian Influenza A Virus Pandemic Preparedness and Vaccine Development

Vaccines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 46 ◽  
Author(s):  
Rory de Vries ◽  
Sander Herfst ◽  
Mathilde Richard
Keyword(s):  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
Vaccine Development ◽  
Influenza Pandemic ◽  
Broad Host Range ◽  
Influenza A Viruses ◽  
Vaccination Strategies ◽  
Pandemic Virus ◽  
Wide Range

Influenza A viruses can infect a wide range of hosts, creating opportunities for zoonotic transmission, i.e., transmission from animals to humans, and placing the human population at constant risk of potential pandemics. In the last hundred years, four influenza A virus pandemics have had a devastating effect, especially the 1918 influenza pandemic that took the lives of at least 40 million people. There is a constant risk that currently circulating avian influenza A viruses (e.g., H5N1, H7N9) will cause a new pandemic. Vaccines are the cornerstone in preparing for and combating potential pandemics. Despite exceptional advances in the design and development of (pre-)pandemic vaccines, there are still serious challenges to overcome, mainly caused by intrinsic characteristics of influenza A viruses: Rapid evolution and a broad host range combined with maintenance in animal reservoirs, making it near impossible to predict the nature and source of the next pandemic virus. Here, recent advances in the development of vaccination strategies to prepare against a pandemic virus coming from the avian reservoir will be discussed. Furthermore, remaining challenges will be addressed, setting the agenda for future research in the development of new vaccination strategies against potentially pandemic influenza A viruses.

scholarly journals Peering Into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

2021 ◽  
Author(s):  
Joshua Yi Yeo ◽  
Samuel Ken-En Gan
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
World Health Organisation ◽  
Resistance Mechanisms ◽  
Human Infection ◽  
World Health ◽  
Influenza A Viruses ◽  
Host Proteins ◽  
Astrakhan Oblast ◽  
Wild Waterfowl

2014 marked the first emergence of avian influenza A(H5N8) in Jeonbuk Province, South Korea, which then quickly spread worldwide. In the midst of the 2020-21 H5N8 outbreak, it spread to domestic poultry and wild waterfowl shorebirds, leading to the first human infection in Astrakhan Oblast, Russia. Despite being clinically asymptomatic and without direct human-to-human transmission, the World Health Organisation stressed the need for continued risk assessment given the nature of Influenza to reassort and generate novel strains. Given its promiscuity and spread to humans, the urgency to understand the mechanisms of possible species jumping to avert disastrous pandemics is increasing. Addressing the epidemiology of H5N8 and its mechanisms of species jumping and its implications, mutational and reassortment libraries can potentially be built, allowing them to be tested on various models complemented with deep-sequencing and automation. With the knowledge on mutational patterns, cellular pathways, drug resistance mechanisms and effects of host proteins can allow better preparedness against H5N8 and other influenza A viruses.

scholarly journals Protection against a Lethal Avian Influenza A Virus in a Mammalian System

1999 ◽  
Vol 73 (2) ◽  
pp. 1453-1459 ◽  
Author(s):  
Janice M. Riberdy ◽  
Kirsten J. Flynn ◽  
Juergen Stech ◽  
Robert G. Webster ◽  
John D. Altman ◽  
...  
Keyword(s):  
T Cell ◽  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Immune Memory ◽  
H3n2 Virus ◽  
Influenza A Viruses ◽  
Cell Responses ◽  
Avian Influenza A Virus

ABSTRACT The question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian H5N1 virus in Hong Kong. The likely strategy would be to vaccinate with a less virulent, laboratory-adapted H5N1 strain isolated previously from birds. Little attention has been given, however, to dissecting the consequences of sequential exposure to serologically related influenza A viruses using contemporary immunology techniques. Such experiments with the H5N1 viruses are limited by the potential risk to humans. An extremely virulent H3N8 avian influenza A virus has been used to infect both immunoglobulin-expressing (Ig+/+) and Ig−/− mice primed previously with a laboratory-adapted H3N2 virus. The cross-reactive antibody response was very protective, while the recall of CD8+ T-cell memory in the Ig−/− mice provided some small measure of resistance to a low-dose H3N8 challenge. The H3N8 virus also replicated in the respiratory tracts of the H3N2-primed Ig+/+ mice, generating secondary CD8+ and CD4+ T-cell responses that may contribute to recovery. The results indicate that the various components of immune memory operate together to provide optimal protection, and they support the idea that related viruses of nonhuman origin can be used as vaccines.

scholarly journals Zoonotic Potential of Currently Circulating Avian Influenza Viruses

2020 ◽  
Vol 39 (1) ◽  
pp. 8-14
Author(s):  
Vladimir Savić
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Human Infection ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Avian Influenza Viruses ◽  
Influenza Pandemics ◽  
Human Infections ◽  
Virus Adaptation ◽  
Efficient Transmission

Over the past and the current centuries, human influenza pandemics have been attributable to viruses with an avian ancestry. Birds are the main source of influenza A viruses and harbour a variety of antigenic subtypes. Certain avian influenza viruses are capable for cross-species transmission including human infections. Although sustained intrehuman transmission of such viruses has not been documented so far, each human infection with avian influenza viruses provides chances for the virus adaptation towards efficient transmission within human population. Here are reviewed currently circulating avian influenza viruses that are of major significance for public health.

scholarly journals The Effects of Genetic Variation on H7N9 Avian Influenza Virus Pathogenicity

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1220
Author(s):  
Szu-Wei Huang ◽  
Sheng-Fan Wang
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Potential Threat ◽  
Amino Acid Insertion ◽  
Live Poultry ◽  
Human Infections

Since the H7N9 avian influenza virus emerged in China in 2013, there have been five seasonal waves which have shown human infections and caused high fatality rates in infected patients. A multibasic amino acid insertion seen in the HA of current H7N9 viruses occurred through natural evolution and reassortment, and created a high pathogenicity avian influenza (HPAI) virus from the low pathogenicity avian influenza (LPAI) in 2017, and significantly increased pathogenicity in poultry, resulting in widespread HPAI H7N9 in poultry, which along with LPAI H7N9, contributed to the severe fifth seasonal wave in China. H7N9 is a novel reassorted virus from three different subtypes of influenza A viruses (IAVs) which displays a great potential threat to public health and the poultry industry. To date, no sustained human-to-human transmission has been recorded by the WHO. However, the high ability of evolutionary adaptation of H7N9 and lack of pre-existing immunity in humans heightens the pandemic potential. Changes in IAVs proteins can affect the viral transmissibility, receptor binding specificity, pathogenicity, and virulence. The multibasic amino acid insertion, mutations in hemagglutinin, deletion and mutations in neuraminidase, and mutations in PB2 contribute to different virological characteristics. This review summarized the latest research evidence to describe the impacts of viral protein changes in viral adaptation and pathogenicity of H7N9, aiming to provide better insights for developing and enhancing early warning or intervention strategies with the goal of preventing highly pathogenic IAVs circulation in live poultry, and transmission to humans.

scholarly journals Future Pandemic Influenza Virus Detection Relies on the Existing Influenza Surveillance Systems: A Perspective from Australia and New Zealand

2019 ◽  
Vol 4 (4) ◽  
pp. 121
Author(s):  
Lance C. Jennings ◽  
Ian G. Barr
Keyword(s):  
New Zealand ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Control Strategies ◽  
Influenza Pandemic ◽  
Virus Detection ◽  
World Health ◽  
Influenza Surveillance ◽  
Surveillance Systems ◽  
Influenza A H1n1

The anniversary of the 1918–1919 influenza pandemic has allowed a refocusing on the global burden of influenza and the importance of co-ordinated international surveillance for both seasonal influenza and the identification of control strategies for future pandemics. Since the introduction of the International Health Regulations (IHR), progress had been slow, until the emergence of the novel influenza A(H1N1)2009 virus and its global spread, which has led to the World Health Organization (WHO) developing a series of guidance documents on global influenza surveillance procedures, severity and risk assessments, and essential measurements for the determination of national pandemic responses. However, the greatest burden of disease from influenza occurs between pandemics during seasonal influenza outbreaks and epidemics. Both Australia and New Zealand utilise seasonal influenza surveillance to support national influenza awareness programs focused on seasonal influenza vaccination education and promotion. These programs also serve to promote the importance of pandemic preparedness.

Increasing the potential ability of human infections in H5N6 avian influenza A viruses

2018 ◽  
Vol 77 (4) ◽  
pp. 349-356 ◽  
Author(s):  
Fucheng Guo ◽  
Tingting Luo ◽  
Zhiqing Pu ◽  
Dan Xiang ◽  
Xuejuan Shen ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Human Infections

scholarly journals Peering into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2276
Author(s):  
Joshua Yi Yeo ◽  
Samuel Ken-En Gan
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Resistance Mechanisms ◽  
Human Infection ◽  
World Health ◽  
Influenza A Viruses ◽  
Host Proteins ◽  
Astrakhan Oblast ◽  
Health Organization ◽  
Wild Waterfowl

2014 marked the first emergence of avian influenza A(H5N8) in Jeonbuk Province, South Korea, which then quickly spread worldwide. In the midst of the 2020–2021 H5N8 outbreak, it spread to domestic poultry and wild waterfowl shorebirds, leading to the first human infection in Astrakhan Oblast, Russia. Despite being clinically asymptomatic and without direct human-to-human transmission, the World Health Organization stressed the need for continued risk assessment given the nature of Influenza to reassort and generate novel strains. Given its promiscuity and easy cross to humans, the urgency to understand the mechanisms of possible species jumping to avert disastrous pandemics is increasing. Addressing the epidemiology of H5N8, its mechanisms of species jumping and its implications, mutational and reassortment libraries can potentially be built, allowing them to be tested on various models complemented with deep-sequencing and automation. With knowledge on mutational patterns, cellular pathways, drug resistance mechanisms and effects of host proteins, we can be better prepared against H5N8 and other influenza A viruses.

scholarly journals A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses

2019 ◽  
Vol 93 (19) ◽  
Author(s):  
Xing Li ◽  
Yamei Gao ◽  
Zhiping Ye
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Receptor Binding ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Single Amino Acid ◽  
Virus Release ◽  
Highly Pathogenic ◽  
H7n9 Influenza ◽  
Human Infections

ABSTRACTThe potential avian influenza pandemic remains a threat to public health, as the avian-origin influenza A(H7N9) virus has caused more than 1,560 laboratory-confirmed human infections since 2013, with nearly 40% mortality. Development of low-pathogenic candidate vaccine viruses (CVVs) for vaccine production is essential for pandemic preparedness. However, the suboptimal growth of CVVs in mammalian cells and chicken eggs is often a challenge. By introducing a single adaptive substitution, G218E, into the hemagglutinin (HA), we generated reassortant A(H7N9)-G218E CVVs that were characterized by significantly enhanced growth in both cells and eggs. These G218E CVVs retained the original antigenicity, as determined by a hemagglutination inhibition assay, and effectively protected ferrets from lethal challenge with the highly pathogenic parental virus. We found that the suboptimal replication of the parental H7 CVVs was associated with impeded progeny virus release as a result of strong HA receptor binding relative to weak neuraminidase (NA) cleavage of receptors. In contrast, the G218E-mediated growth improvement was attributed to relatively balanced HA and NA functions, resulted from reduced HA binding to both human- and avian-type receptors, and thus facilitated NA-mediated virus release. Our findings revealed that a single amino acid mutation at residue 218 of the HA improved the growth of A(H7N9) influenza virus by balancing HA and NA functions, shedding light on an alternative approach for optimizing certain influenza CVVs.IMPORTANCEThe circulating avian influenza A(H7N9) has caused recurrent epidemic waves with high mortality in China since 2013, in which the alarming fifth wave crossing 2016 and 2017 was highlighted by a large number of human infections and the emergence of highly pathogenic avian influenza (HPAI) A(H7N9) strains in human cases. We generated low-pathogenic reassortant CVVs derived from the emerging A(H7N9) with improved virus replication and protein yield in both MDCK cells and eggs by introducing a single substitution, G218E, into HA, which was associated with reducing HA receptor binding and subsequently balancing HA-NA functions. Thein vitroandin vivoexperiments demonstrated comparable antigenicity of the G218E CVVs with that of their wild-type (WT) counterparts, and both the WT and the G218E CVVs fully protected ferrets from parental HPAI virus challenge. With high yield traits and the anticipated antigenicity, the G218E CVVs should benefit preparedness against the threat of an A(H7N9) influenza pandemic.

Hemagglutinins of avian influenza viruses are proteolytically activated by TMPRSS2 in human and murine airway cells

2021 ◽  
Author(s):  
Dorothea Bestle ◽  
Hannah Limburg ◽  
Diana Kruhl ◽  
Anne Harbig ◽  
David A. Stein ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Cleavage Site ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Avian Influenza Viruses ◽  
Proteolytic Activation ◽  
Human Infections ◽  
Human And Mouse ◽  
Airway Cells

Cleavage of the influenza A virus (IAV) hemagglutinin (HA) by host proteases is indispensable for virus replication. Most IAVs possess a monobasic HA cleavage site cleaved by trypsin-like proteases. Previously, the transmembrane protease TMPRSS2 was shown to be essential for proteolytic activation of IAV HA subtypes H1, H2, H7 and H10 in mice. In contrast, additional proteases are involved in activation of certain H3 IAVs, indicating that HAs with monobasic cleavage site can differ in their sensitivity to host proteases. Here, we investigated the role of TMPRSS2 in proteolytic activation of avian HA subtypes H1 to H11 and H14 to H16 in human and mouse airway cell cultures. Using reassortant viruses carrying representative HAs, we analysed HA cleavage and multicycle replication in (i) lung cells of TMPRSS2-deficient mice and (ii) Calu-3 cells and primary human bronchial cells subjected to morpholino oligomer-mediated knockdown of TMPRSS2 activity. TMPRSS2 was found to be crucial for activation of H1 to H11, H14 and H15 in airway cells of human and mouse. Only H9 with an R-S-S-R cleavage site and H16 were proteolytically activated in the absence of TMPRSS2 activity, albeit with reduced efficiency. Moreover, a TMPRSS2-orthologous protease from duck supported activation of H1 to H11, H15 and H16 in MDCK cells. Together, our data demonstrate that in human and murine respiratory cells, TMPRSS2 is the major activating protease of almost all IAV HA subtypes with monobasic cleavage site. Furthermore, our results suggest that TMPRSS2 supports activation of IAV with monobasic cleavage site in ducks. Importance Human infections with avian influenza A viruses upon exposure to infected birds are frequently reported and have received attention as a potential pandemic threat. Cleavage of the envelope glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion and essential for virus infectivity. In this study, we identify the transmembrane protease TMPRSS2 as the major activating protease of avian influenza virus HAs of subtypes H1 to H11, H14 and H15 in human and murine airway cells. Our data demonstrate that inhibition of TMPRSS2 activity may provide a useful approach for the treatment of human infections with avian influenza viruses that should be considered for pandemic preparedness as well. Additionally, we show that a TMPRSS2-orthologous protease from duck can activate avian influenza virus HAs with a monobasic cleavage site and thus represents a potential virus-activating protease in waterfowl, the primary reservoir for influenza A viruses.

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