scholarly journals Are Ducks Contributing to the Endemicity of Highly Pathogenic H5N1 Influenza Virus in Asia?

2005 ◽  
Vol 79 (17) ◽  
pp. 11269-11279 ◽  
Author(s):  
K. M. Sturm-Ramirez ◽  
D. J. Hulse-Post ◽  
E. A. Govorkova ◽  
J. Humberd ◽  
P. Seiler ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Virus Disease ◽  
Influenza Viruses ◽  
H5n1 Influenza Virus ◽  
Highly Pathogenic ◽  
Main Site ◽  
H5n1 Influenza ◽  
Pathogenic H5n1 ◽  
Virus Isolates

ABSTRACT Wild waterfowl are the natural reservoir of all influenza A viruses, and these viruses are usually nonpathogenic in these birds. However, since late 2002, H5N1 outbreaks in Asia have resulted in mortality among waterfowl in recreational parks, domestic flocks, and wild migratory birds. The evolutionary stasis between influenza virus and its natural host may have been disrupted, prompting us to ask whether waterfowl are resistant to H5N1 influenza virus disease and whether they can still act as a reservoir for these viruses. To better understand the biology of H5N1 viruses in ducks and attempt to answer this question, we inoculated juvenile mallards with 23 different H5N1 influenza viruses isolated in Asia between 2003 and 2004. All virus isolates replicated efficiently in inoculated ducks, and 22 were transmitted to susceptible contacts. Viruses replicated to higher levels in the trachea than in the cloaca of both inoculated and contact birds, suggesting that the digestive tract is not the main site of H5N1 influenza virus replication in ducks and that the fecal-oral route may no longer be the main transmission path. The virus isolates' pathogenicities varied from completely nonpathogenic to highly lethal and were positively correlated with tracheal virus titers. Nevertheless, the eight virus isolates that were nonpathogenic in ducks replicated and transmitted efficiently to naïve contacts, suggesting that highly pathogenic H5N1 viruses causing minimal signs of disease in ducks can propagate silently and efficiently among domestic and wild ducks in Asia and that they represent a serious threat to human and veterinary public health.

scholarly journals Characterization of a Highly Pathogenic H5N1 Avian Influenza A Virus Isolated from Duck Meat

2002 ◽  
Vol 76 (12) ◽  
pp. 6344-6355 ◽  
Author(s):  
Terrence M. Tumpey ◽  
David L. Suarez ◽  
Laura E. L. Perkins ◽  
Dennis A. Senne ◽  
Jae-gil Lee ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Influenza A Virus ◽  
Influenza A ◽  
Infectious Virus ◽  
Influenza Viruses ◽  
H5n1 Influenza Virus ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1

ABSTRACT Since the 1997 H5N1 influenza virus outbreak in humans and poultry in Hong Kong, the emergence of closely related viruses in poultry has raised concerns that additional zoonotic transmissions of influenza viruses from poultry to humans may occur. In May 2001, an avian H5N1 influenza A virus was isolated from duck meat that had been imported to South Korea from China. Phylogenetic analysis of the hemagglutinin (HA) gene of A/Duck/Anyang/AVL-1/01 showed that the virus clustered with the H5 Goose/Guandong/1/96 lineage and 1997 Hong Kong human isolates and possessed an HA cleavage site sequence identical to these isolates. Following intravenous or intranasal inoculation, this virus was highly pathogenic and replicated to high titers in chickens. The pathogenesis of DK/Anyang/AVL-1/01 virus in Pekin ducks was further characterized and compared with a recent H5N1 isolate, A/Chicken/Hong Kong/317.5/01, and an H5N1 1997 chicken isolate, A/Chicken/Hong Kong/220/97. Although no clinical signs of disease were observed in H5N1 virus-inoculated ducks, infectious virus could be detected in lung tissue, cloacal, and oropharyngeal swabs. The DK/Anyang/AVL-1/01 virus was unique among the H5N1 isolates in that infectious virus and viral antigen could also be detected in muscle and brain tissue of ducks. The pathogenesis of DK/Anyang/AVL-1/01 virus was characterized in BALB/c mice and compared with the other H5N1 isolates. All viruses replicated in mice, but in contrast to the highly lethal CK/HK/220/97 virus, DK/Anyang/AVL-1/01 and CK/HK/317.5/01 viruses remained localized to the respiratory tract. DK/Anyang/AVL-1/01 virus caused weight loss and resulted in 22 to 33% mortality, whereas CK/HK/317.5/01-infected mice exhibited no morbidity or mortality. The isolation of a highly pathogenic H5N1 influenza virus from poultry indicates that such viruses are still circulating in China and may present a risk for transmission of the virus to humans.

scholarly journals A Highly Pathogenic H5N1 Influenza A Virus Isolated from a Flamingo on the Caspian Sea Shore

2020 ◽  
Vol 9 (39) ◽  
Author(s):  
Kobey Karamendin ◽  
Aidyn Kydyrmanov ◽  
Yermukhammet Kasymbekov ◽  
Klara Daulbayeva ◽  
Elizaveta Khan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Caspian Sea ◽  
Influenza A ◽  
Influenza Viruses ◽  
H5n1 Influenza Virus ◽  
Avian Influenza Viruses ◽  
The Caspian Sea ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1

ABSTRACT In 2015, in the Kazakh part of the northern Caspian Sea region, during the monitoring of wild birds for avian influenza viruses, a highly pathogenic A/flamingo/Mangistau/6570/2015(H5N1) influenza virus was isolated from a dead flamingo. This study aimed to obtain the complete genome sequence of the isolate.

scholarly journals Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice

2009 ◽  
Vol 83 (20) ◽  
pp. 10417-10426 ◽  
Author(s):  
Adrianus C. M. Boon ◽  
Jennifer deBeauchamp ◽  
Anna Hollmann ◽  
Jennifer Luke ◽  
Malak Kotb ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H5n1 Virus ◽  
Lethal Dose ◽  
Influenza Virus Infection ◽  
Virus Titer ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1

ABSTRACT Despite the prevalence of H5N1 influenza viruses in global avian populations, comparatively few cases have been diagnosed in humans. Although viral factors almost certainly play a role in limiting human infection and disease, host genetics most likely contribute substantially. To model host factors in the context of influenza virus infection, we determined the lethal dose of a highly pathogenic H5N1 virus (A/Hong Kong/213/03) in C57BL/6J and DBA/2J mice and identified genetic elements associated with survival after infection. The lethal dose in these hosts varied by 4 logs and was associated with differences in replication kinetics and increased production of proinflammatory cytokines CCL2 and tumor necrosis factor alpha in susceptible DBA/2J mice. Gene mapping with recombinant inbred BXD strains revealed five loci or Qivr (quantitative trait loci for influenza virus resistance) located on chromosomes 2, 7, 11, 15, and 17 associated with resistance to H5N1 virus. In conjunction with gene expression profiling, we identified a number of candidate susceptibility genes. One of the validated genes, the hemolytic complement gene, affected virus titer 7 days after infection. We conclude that H5N1 influenza virus-induced pathology is affected by a complex and multigenic host component.

scholarly journals An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection

2015 ◽  
Vol 89 (8) ◽  
pp. 4549-4561 ◽  
Author(s):  
Mark Zanin ◽  
Zhen-Yong Keck ◽  
G. Jonah Rainey ◽  
Chia-Ying Kao Lam ◽  
Adrianus C. M. Boon ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Therapeutic Agent ◽  
Influenza Viruses ◽  
H5n1 Influenza Virus ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Prophylactic Dose ◽  
H5n1 Avian Influenza ◽  
Pathogenic H5n1

ABSTRACTHighly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. While vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. To produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted H5N1 influenza viruses, we developed two neutralizing monoclonal antibodies and combined them into a single bispecific Fc fusion protein (the Fc dual-affinity retargeting [FcDART] molecule). In mice, a single therapeutic or prophylactic dose of either monoclonal antibody at 2.5 mg/kg of body weight provided 100% protection against challenge with A/Vietnam/1203/04 (H5N1) or the antigenically drifted strain A/Whooper swan/Mongolia/244/05 (H5N1). In ferrets, a single 1-mg/kg prophylactic dose provided 100% protection against A/Vietnam/1203/04 challenge. FcDART was also effective, as a single 2.5-mg/kg therapeutic or prophylactic dose in mice provided 100% protection against A/Vietnam/1203/04 challenge. Antibodies bound to conformational epitopes in antigenic sites on the globular head of the hemagglutinin protein, on the basis of analysis of mutants with antibody escape mutations. While it was possible to generate escape mutantsin vitro, they were neutralized by the antibodiesin vivo, as mice infected with escape mutants were 100% protected after only a single therapeutic dose of the antibody used to generate the escape mutantin vitro. In summary, we have combined the antigen specificities of two highly efficacious anti-H5N1 influenza virus antibodies into a bispecific FcDART molecule, which represents a strategy to produce broadly neutralizing antibodies that are effective against antigenically diverse influenza viruses.IMPORTANCEHighly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and are a pandemic threat. A vaccine is available, but other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. The variability of the virus means that such an approach must be broad spectrum. To achieve this, we developed two antibodies that neutralize H5N1 influenza viruses. In mice, these antibodies provided complete protection against a spectrum of H5N1 influenza viruses at a single low dose. We then combined the two antibodies into a single molecule, FcDART, which combined the broad-spectrum activity and protective efficacy of both antibodies. This treatment provides a novel and effective therapeutic agent or prophylactic with activity against highly pathogenic H5N1 avian influenza viruses.

Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus

2007 ◽  
Vol 79 (6) ◽  
pp. 811-819 ◽  
Author(s):  
Takeshi Ichinohe ◽  
Noriyo Nagata ◽  
Peter Strong ◽  
Shin-ichi Tamura ◽  
Hidehiro Takahashi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
H5n1 Influenza Virus ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1

scholarly journals Neuraminidase Inhibitor Sensitivity and Receptor-Binding Specificity of Cambodian Clade 1 Highly Pathogenic H5N1 Influenza Virus

2011 ◽  
Vol 55 (5) ◽  
pp. 2004-2010 ◽  
Author(s):  
M. Naughtin ◽  
J. C. Dyason ◽  
S. Mardy ◽  
S. Sorn ◽  
M. von Itzstein ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Receptor Binding ◽  
Reverse Genetics ◽  
Binding Specificity ◽  
Neuraminidase Inhibitor ◽  
H5n1 Influenza Virus ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Receptor Binding Specificity ◽  
Pathogenic H5n1

ABSTRACTThe evolution of the highly pathogenic H5N1 influenza virus produces genetic variations that can lead to changes in antiviral susceptibility and in receptor-binding specificity. In countries where the highly pathogenic H5N1 virus is endemic or causes regular epidemics, the surveillance of these changes is important for assessing the pandemic risk. In Cambodia between 2004 and 2010, there have been 26 outbreaks of highly pathogenic H5N1 influenza virus in poultry and 10 reported human cases, 8 of which were fatal. We have observed naturally occurring mutations in hemagglutinin (HA) and neuraminidase (NA) of Cambodian H5N1 viruses that were predicted to alter sensitivity to neuraminidase inhibitors (NAIs) and/or receptor-binding specificity. We tested H5N1 viruses isolated from poultry and humans between 2004 and 2010 for sensitivity to the NAIs oseltamivir (Tamiflu) and zanamivir (Relenza). All viruses were sensitive to both inhibitors; however, we identified a virus with a mildly decreased sensitivity to zanamivir and have predicted that a V149A mutation is responsible. We also identified a virus with a hemagglutinin A134V mutation, present in a subpopulation amplified directly from a human sample. Using reverse genetics, we verified that this mutation is adaptative for human α2,6-linked sialidase receptors. The importance of an ongoing surveillance of H5N1 antigenic variance and genetic drift that may alter receptor binding and sensitivities of H5N1 viruses to NAIs cannot be underestimated while avian influenza remains a pandemic threat.

scholarly journals Epitope Mapping of the Hemagglutinin Molecule of a Highly Pathogenic H5N1 Influenza Virus by Using Monoclonal Antibodies

2007 ◽  
Vol 81 (23) ◽  
pp. 12911-12917 ◽  
Author(s):  
Nikolai V. Kaverin ◽  
Irina A. Rudneva ◽  
Elena A. Govorkova ◽  
Tatyana A. Timofeeva ◽  
Aleksandr A. Shilov ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
H5n1 Virus ◽  
Antigenic Site ◽  
H5n1 Influenza Virus ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Antigenic Sites ◽  
Escape Mutants ◽  
Pathogenic H5n1

ABSTRACT We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus containing A/Vietnam/1203/04 (H5N1) ΔHA and neuraminidase genes in the genetic background of A/Puerto Rico/8/34 (H1N1) virus. The mutants were selected with a panel of eight anti-HA monoclonal antibodies (MAbs), seven to A/Vietnam/1203/04 (H5N1) virus and one to A/Chicken/Pennsylvania/8125/83 (H5N2) virus, and the mutants’ HA genes were sequenced. The amino acid changes suggested three MAb groups: four MAbs reacted with the complex epitope comprising parts of the antigenic site B of H3 HA and site Sa of H1 HA, two MAbs reacted with the epitope corresponding to the antigenic site A in H3 HA, and two MAbs displayed unusual behavior: each recognized amino acid changes at two widely separate antigenic sites. Five changes were detected in amino acid residues not previously reported as changed in H5 escape mutants, and four others had substitutions not previously described. The HA antigenic structure differs substantially between A/Vietnam/1203/04 (H5N1) virus and the low-pathogenic A/Mallard/Pennsylvania/10218/84 (H5N2) virus we previously characterized (N. V. Kaverin et al., J. Gen. Virol. 83:2497-2505, 2002). The hemagglutination inhibition reactions of the MAbs with recent highly pathogenic H5N1 viruses were consistent with the antigenic-site amino acid changes but not with clades and subclades based on H5 phylogenetic analysis. These results provide information on the recognition sites of the MAbs widely used to study H5N1 viruses and demonstrate the involvement of the HA antigenic sites in the evolution of highly pathogenic H5N1 viruses, findings that can be critical for characterizing pathogenesis and vaccine design.

scholarly journals Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice

2018 ◽  
Vol 14 (1) ◽  
pp. e1006821 ◽  
Author(s):  
Hui Li ◽  
Konrad C. Bradley ◽  
Jason S. Long ◽  
Rebecca Frise ◽  
Jonathan W. Ashcroft ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Replication ◽  
Myeloid Cells ◽  
H5n1 Influenza Virus ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1
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