scholarly journals A Critical Prospect of Structural Designing of Avian Influenza A/H5N1 Neuraminidase Inhibitors That Evade Tamiflu Resistance

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Petar M. Mitrasinovic
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Rational Design ◽  
Influenza Pandemic ◽  
Health Concern ◽  
Structural Basis ◽  
Neuraminidase Inhibitors ◽  
Virus Spread ◽  
Public Health Concern ◽  
Flu Vaccine

The key public health concern is to define the way in which the next influenza pandemic will be controlled. At present, the question of vital importance is: in the absence of a specific avian flu vaccine, could antiviral drugs obstruct a pandemic should the virus spread from birds to humans? The answer to the issue is inevitably related to finding the ways to circumvent Tamiflu resistance that is well documented in the literature. Several remarkable but slightly mutually inconsistent contributions have been recently reported with the aim to facilitate the development of new inhibitors acting on the key target—neuraminidase of avian influenza A/H5N1 virus. Herein, the versatile arguments are critically analyzed and reconciled. Consequently, the most relevant structural basis for the rational design of novel antivirals is elaborated.

scholarly journals Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Hua Yang ◽  
Paul J. Carney ◽  
Jessie C. Chang ◽  
Zhu Guo ◽  
James Stevens
Keyword(s):  
Public Health ◽  
Avian Influenza ◽  
Influenza A ◽  
Human Infection ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Health Concern ◽  
Public Health Concern ◽  
H7n9 Influenza ◽  
Epidemic Wave

ABSTRACTThe avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that, compared to the 2013 virus HAs, the fifth-wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9) HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth-wave H7 HAs analyzed in this study.IMPORTANCEThe A(H7N9) viruses circulating in China are of great public health concern. Here, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.

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 Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential

1998 ◽  
Vol 72 (9) ◽  
pp. 7367-7373 ◽  
Author(s):  
Toshihiro Ito ◽  
J. Nelson S. S. Couceiro ◽  
Sørge Kelm ◽  
Linda G. Baum ◽  
Scott Krauss ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Influenza Viruses ◽  
Structural Basis ◽  
Human Populations ◽  
Influenza A Viruses ◽  
Human Virus ◽  
Surface Receptors ◽  
Virus Receptors ◽  
Avian Influenza A Virus

ABSTRACT Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.

scholarly journals Bangladeshi backyard poultry raisers’ perceptions and practices related to zoonotic transmission of avian influenza

2011 ◽  
Vol 6 (02) ◽  
pp. 156-165 ◽  
Author(s):  
Rebeca Sultana ◽  
Nadia Ali Rimi ◽  
Shamim Azad ◽  
M. Saiful Islam ◽  
M. Salah Uddin Khan ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Low Income ◽  
Disease Transmission ◽  
Close Contact ◽  
Influenza Pandemic ◽  
Health Concern ◽  
Financial Loss ◽  
Bird Flu ◽  
Require Time ◽  
Backyard Poultry

Introduction: Highly pathogenic avian influenza (H5N1) virus (known as "bird flu") is an important public health concern due to its potential to infect humans and cause a human pandemic. Bangladesh is a high-risk country for an influenza pandemic because of its dense human population, widespread backyard poultry raising, and endemic H5N1 infection in poultry. Understanding poultry raisers' perceived risks and identifying their risk exposures can help to develop interventions to reduce the risk of avian influenza transmission. This paper explores the perception of Bangladeshi backyard poultry raisers regarding poultry sickness and zoonotic disease transmission and relevant practices. Methodology: We conducted a qualitative study using social mapping (n=2), in-depth interviews (n=40), household mapping (n=40) and observation (n=16), in two backyard poultry-raising communities. Results: The poultry raisers recognized various signs of poultry illness but they did not distinguish among diseases using biomedical classifications. They perceived disease transmission from poultry to poultry, but not from poultry to humans. They usually kept sick poultry under the bed. If the poultry did not recover, they were slaughtered and consumed or sold. The poultry raisers had close contact with sick birds while handling and slaughtering poultry. Conclusions: The poultry raisers are unlikely to follow instructions from health authorities to prevent "bird flu" transmission because many of the instructions ask low-income producers to change their existing practices and require time, money, and financial loss. Villagers are more likely to comply with interventions that help to protect their flocks and address their financial interest.

scholarly journals Bird Flu, the Hanging Pandemic Threat for Human - It's Risk Assessment and Containment

1970 ◽  
Vol 25 (1) ◽  
pp. 1-8
Author(s):  
M Anwar Hossain ◽  
M Intakhar Ahmad ◽  
M Manjurul Karim
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Perfect Match ◽  
Influenza Viruses ◽  
Environment Management ◽  
Bird Flu ◽  
Recognition Specificity ◽  
Pandemic Threat ◽  
To Come

Bird flu, synonym of avian influenza (AI) caused by influenza A virus, become concern across the world for the possible incidence of the next human influenza pandemic. The latent danger of AI pandemic remains very real, though, the precise timing of occurrence and severity is uncertain. Each avian influenza type A (AIA) contains one of the 16 subtypes of haemagglutinin (HA) and 9 neuraminidases (NA) implicating theoretically 144 subtypes of AIA are possible in circulation, but only H1N1, H2N2 and H3N2 subtypes are documented for past pandemics in humans. In recent years H5N1, H7N3, H7N2, H7N7 and H9N2 are isolated from human samples, though H1N1 and H3N2 are still in circulation. Avian influenza viruses preferentially recognize receptor containing sialosugar chains terminating in sialic acid ?-2,3-galactose in bird, whereas, human preferentially contain ?-2,6-galactose subtype-receptor. To initiate a pandemic outbreak in human, the AIA viruses need alteration of receptor recognition specificity; and perfect match between HA and NA along with optimal cellular tropism. Cyclic nature of bird-flu emergence, and moreover, sporadic human incident reported around Asia and Europe in recent years anticipating a pandemic appearance of bird-flu in time to come. As we are on the edge of this alarming situation, AI prevention and containment can be considered under categories of surveillance, intervention, antiviral drugs, vaccination together with environment management issues.Keywords: Pandemic; Avian influenza; Genetic reassortment; Host specificity; Environment management  DOI: http://dx.doi.org/10.3329/bjm.v25i1.4847Bangladesh J Microbiol, Volume 25, Number 1, June 2008, pp 1-8

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 Antiviral Susceptibility of Variant Influenza A(H3N2)v Viruses Isolated in the United States from 2011 to 2013

2014 ◽  
Vol 58 (4) ◽  
pp. 2045-2051 ◽  
Author(s):  
K. Sleeman ◽  
V. P. Mishin ◽  
Z. Guo ◽  
R. J. Garten ◽  
A. Balish ◽  
...  
Keyword(s):  
United States ◽  
Influenza A ◽  
Untreated Patient ◽  
Continuous Monitoring ◽  
The United States ◽  
Antiviral Drugs ◽  
Influenza Viruses ◽  
Health Concern ◽  
Public Health Concern ◽  
M Gene

ABSTRACTSince 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n= 168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs.

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 Co-infection of SARS-CoV-2 and influenza virus causes more severe and prolonged pneumonia in hamsters

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takaaki Kinoshita ◽  
Kenichi Watanabe ◽  
Yasuteru Sakurai ◽  
Kodai Nishi ◽  
Rokusuke Yoshikawa ◽  
...  
Keyword(s):  
Public Health ◽  
Health Risks ◽  
Influenza A ◽  
Body Weight Loss ◽  
The Other ◽  
Health Concern ◽  
Public Health Concern ◽  
A Cell ◽  
Immunohistochemical Analyses

AbstractCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a serious public health concern worldwide. Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10 days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases.

Sign in / Sign up

Export Citation Format

Share Document