scholarly journals Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model

2007 ◽  
Vol 81 (13) ◽  
pp. 6890-6898 ◽  
Author(s):  
Hui-Ling Yen ◽  
Aleksandr S. Lipatov ◽  
Natalia A. Ilyushina ◽  
Elena A. Govorkova ◽  
John Franks ◽  
...  
Keyword(s):  
Hong Kong ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Clinical Signs ◽  
Influenza Viruses ◽  
Contact Model ◽  
Virus Shedding ◽  
H5n1 Influenza

ABSTRACT The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with α2,3 or α2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess “avian-like” α2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 103 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for “human-like” α2,6-linked SA receptors in addition to their affinity for α2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to the ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any clinical signs or detectable virus shedding. In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species.

scholarly journals Reemerging H5N1 Influenza Viruses in Hong Kong in 2002 Are Highly Pathogenic to Ducks

2004 ◽  
Vol 78 (9) ◽  
pp. 4892-4901 ◽  
Author(s):  
Katharine M. Sturm-Ramirez ◽  
Trevor Ellis ◽  
Barry Bousfield ◽  
Lucy Bissett ◽  
Kitman Dyrting ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Neurological Dysfunction ◽  
Aquatic Birds ◽  
Antigenic Analysis ◽  
Highly Pathogenic ◽  
H5n1 Influenza

ABSTRACT Waterfowl are the natural reservoir of all influenza A viruses, which are usually nonpathogenic in wild aquatic birds. However, in late 2002, outbreaks of highly pathogenic H5N1 influenza virus caused deaths among wild migratory birds and resident waterfowl, including ducks, in two Hong Kong parks. In February 2003, an avian H5N1 virus closely related to one of these viruses was isolated from two humans with acute respiratory distress, one of whom died. Antigenic analysis of the new avian isolates showed a reactivity pattern different from that of H5N1 viruses isolated in 1997 and 2001. This finding suggests that significant antigenic variation has recently occurred among H5N1 viruses. We inoculated mallards with antigenically different H5N1 influenza viruses isolated between 1997 and 2003. The new 2002 avian isolates caused systemic infection in the ducks, with high virus titers and pathology in multiple organs, particularly the brain. Ducks developed acute disease, including severe neurological dysfunction and death. Virus was also isolated at high titers from the birds' drinking water and from contact birds, demonstrating efficient transmission. In contrast, H5N1 isolates from 1997 and 2001 were not consistently transmitted efficiently among ducks and did not cause significant disease. Despite a high level of genomic homology, the human isolate showed striking biological differences from its avian homologue in a duck model. This is the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.

scholarly journals Avian influenza viruses - new causative a gents of human infections

2006 ◽  
Vol 59 (1-2) ◽  
pp. 29-32 ◽  
Author(s):  
Ivana Hrnjakovic-Cvjetkovic ◽  
Dejan Cvjetkovic ◽  
Vera Jerant-Patic ◽  
Vesna Milosevic ◽  
Jelena Tadic-Radovanov ◽  
...  
Keyword(s):  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A ◽  
H5n1 Virus ◽  
Influenza Viruses ◽  
Control Measures ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Avian Influenza Viruses ◽  
H5n1 Influenza

Introduction. Influenza A viruses can infect humans, some mammals and especially birds. Subtypes of human influenza A viruses: ACH1N1), ACH2N2) and A(H3N2) have caused pandemics. Avian influenza viruses vary owing to their 15 hemagglutinins (H) and 9 neuraminidases (N). Human cases of avian influenza A In the Netherlands in 2003, there were 83 human cases of influenza A (H7N7). In 1997, 18 cases of H5N1 influenza A, of whom 6 died, were found among residents of Hong Kong. In 2004, 34 human cases (23 deaths) were reported in Viet Nam and Thailand. H5N1 virus-infected patients presented with fever and respiratory symptoms. Complications included respiratory distress syndrome, renal failure, liver dysfunction and hematologic disorders. Since 1999, 7 cases of human influenza H9N2 infection have been identified in China and Hong Kong. The importance of human infection with avian influenza viruses. H5N1 virus can directly infect humans. Genetic reassortment of human and avian influenza viruses may occur in humans co infected with current human A(HIN1) or A(H3N2) subtypes and avian influenza viruses. The result would be a new influenza virus with pandemic potential. All genes of H5Nl viruses isolated from humans are of avian origin. Prevention and control. The reassortant virus containing H and N from avian and the remaining proteins from human influenza viruses will probably be used as a vaccine strain. The most important control measures are rapid destruction of all infected or exposed birds and rigorous disinfection of farms. Individuals exposed to suspected animals should receive prophylactic treatment with antivirals and annual vaccination. .

scholarly journals Efficacy of Zanamivir against Avian Influenza A Viruses That Possess Genes Encoding H5N1 Internal Proteins and Are Pathogenic in Mammals

2001 ◽  
Vol 45 (4) ◽  
pp. 1216-1224 ◽  
Author(s):  
Irina A. Leneva ◽  
Olga Goloubeva ◽  
Robert J. Fenton ◽  
Margaret Tisdale ◽  
Robert G. Webster
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A ◽  
Influenza Viruses ◽  
Interspecies Transmission ◽  
H9n2 Influenza Virus ◽  
H5n1 Influenza ◽  
Genes Encoding ◽  
The Brain

ABSTRACT In 1997, an avian H5N1 influenza virus, A/Hong Kong/156/97 (A/HK/156/97), caused six deaths in Hong Kong, and in 1999, an avian H9N2 influenza virus infected two children in Hong Kong. These viruses and a third avian virus [A/Teal/HK/W312/97 (H6N1)] have six highly related genes encoding internal proteins. Additionally, A/Chicken/HK/G9/97 (H9N2) virus has PB1 and PB2 genes that are highly related to those of A/HK/156/97 (H5N1), A/Teal/HK/W312/97 (H6N1), and A/Quail/HK/G1/97 (H9N2) viruses. Because of their similarities with the H5N1 virus, these H6N1 and H9N2 viruses may have the potential for interspecies transmission. We demonstrate that these H6N1 and H9N2 viruses are pathogenic in mice but that their pathogenicities are less than that of A/HK/156/97 (H5N1). Unadapted virus replicated in lungs, but only A/HK/156/97 (H5N1) was found in the brain. After three passages (P3) in mouse lungs, the pathogenicity of the viruses increased, with both A/Teal/HK/W312/97 (H6N1) (P3) and A/Quail/HK/G1/97 (H9N2) (P3) viruses being found in the brain. The neuraminidase inhibitor zanamivir inhibited viral replication in Madin-Darby canine kidney cells in virus yield assays (50% effective concentration, 8.5 to 14.0 μM) and inhibited viral neuraminidase activity (50% inhibitory concentration, 5 to 10 nM). Twice daily intranasal administration of zanamivir (50 and 100 mg/kg of body weight) completely protected infected mice from death. At a dose of 10 mg/kg, zanamivir completely protected mice from infection with H9N2 viruses and increased the mean survival day and the number of survivors infected with H6N1 and H5N1 viruses. Zanamivir, at all doses tested, significantly reduced the virus titers in the lungs and completely blocked the spread of virus to the brain. Thus, zanamivir is efficacious in treating avian influenza viruses that can be transmitted to mammals.

scholarly journals Pandemic Threat Posed by Avian Influenza A Viruses

2001 ◽  
Vol 14 (1) ◽  
pp. 129-149 ◽  
Author(s):  
Taisuke Horimoto ◽  
Yoshihiro Kawaoka
Keyword(s):  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A ◽  
Mammalian Species ◽  
Influenza Viruses ◽  
Human Populations ◽  
Avian Influenza Viruses ◽  
Influenza Pandemics ◽  
Avian Virus ◽  
H5n1 Influenza

SUMMARY Influenza pandemics, defined as global outbreaks of the disease due to viruses with new antigenic subtypes, have exacted high death tolls from human populations. The last two pandemics were caused by hybrid viruses, or reassortants, that harbored a combination of avian and human viral genes. Avian influenza viruses are therefore key contributors to the emergence of human influenza pandemics. In 1997, an H5N1 influenza virus was directly transmitted from birds in live poultry markets in Hong Kong to humans. Eighteen people were infected in this outbreak, six of whom died. This avian virus exhibited high virulence in both avian and mammalian species, causing systemic infection in both chickens and mice. Subsequently, another avian virus with the H9N2 subtype was directly transmitted from birds to humans in Hong Kong. Interestingly, the genes encoding the internal proteins of the H9N2 virus are genetically highly related to those of the H5N1 virus, suggesting a unique property of these gene products. The identification of avian viruses in humans underscores the potential of these and similar strains to produce devastating influenza outbreaks in major population centers. Although highly pathogenic avian influenza viruses had been identified before the 1997 outbreak in Hong Kong, their devastating effects had been confined to poultry. With the Hong Kong outbreak, it became clear that the virulence potential of these viruses extended to humans.

scholarly journals Characterization of human influenza A (H5N1) virus infection in mice: neuro-, pneumo- and adipotropic infection

2000 ◽  
Vol 81 (10) ◽  
pp. 2503-2510 ◽  
Author(s):  
Hidekazu Nishimura ◽  
Shigeyuki Itamura ◽  
Takuya Iwasaki ◽  
Takeshi Kurata ◽  
Masato Tashiro
Keyword(s):  
Hong Kong ◽  
Influenza A ◽  
Degenerative Change ◽  
Lethal Dose ◽  
Virus Antigen ◽  
Influenza Viruses ◽  
Adipose Tissues ◽  
H5n1 Influenza ◽  
The Brain

Mice (ddY strain, 4 weeks old) were infected intranasally with the H5N1 influenza viruses A/Hong Kong/156/97 (HK156) and A/Hong Kong/483/97 (HK483) isolated from humans. HK156 and HK483 required 200 and 5 p.f.u. of virus, respectively, to give a 50% lethal dose to the mice when the volume of inoculum was set at 10 μl. Both viruses caused encephalitis and severe bronchopneumonia in infected mice. The severity of lung lesions caused by the viruses was essentially similar, whereas HK483 caused more extensive lesions in the brain than did HK156. This was supported by the results of virus titration of organ homogenates, which showed that the virus titres in brains of HK483-infected mice were more than 100-fold higher than those of HK156-infected mice, while those in lungs were almost equivalent. Both viruses were detected in homogenates of the heart, liver, spleen and kidney and blood of the infected mice. Virus antigen was detected by immunohistology in the heart and liver, albeit sporadically, but caused no degenerative change in these organs. The antigen was not detected in the thymus, spleen, pancreas, kidney or gastrointestinal tract. In contrast, virus antigen was found frequently in adipose tissues attached to those organs. The adipose tissues showed severe degenerative change and the virus titres in the tissues were high and comparable to those in lungs. Thus, infection of HK156 and HK483 in our mouse model was pneumo-, neuro- and adipotropic, but not pantropic. Furthermore, HK483 showed higher neurotropism than HK156, which may account for its higher lethality.

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 Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses

Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1283-1291 ◽  
Author(s):  
Nadia Naffakh ◽  
Pascale Massin ◽  
Nicolas Escriou ◽  
Bernadette Crescenzo-Chaigne ◽  
Sylvie van der Werf
Keyword(s):  
Hong Kong ◽  
Influenza A ◽  
Genetic System ◽  
Influenza Viruses ◽  
Molecular Characteristics ◽  
Influenza A Viruses ◽  
Human Virus ◽  
H5n1 Influenza ◽  
Core Proteins

In order to determine how efficiently the polymerase proteins derived from human and avian influenza A viruses can interact with each other in the context of a mammalian cell, a genetic system that allows the in vivo reconstitution of active ribonucleoproteins was used. The ability to achieve replication of a viral-like reporter RNA in COS-1 cells was examined with heterospecific mixtures of the core proteins (PB1, PB2, PA and NP) from two strains of human viruses (A/Puerto Rico/8/34 and A/Victoria/3/75), two strains of avian viruses (A/Mallard/NY/6750/78 and A/FPV/-Rostock/34), and a strain of avian origin (A/Hong Kong/156/97) that was isolated from the first human case of H5N1 influenza in Hong Kong in 1997. In accordance with published observations on reassortant viruses, PB2 amino acid 627 was identified as a major determinant of the replication efficiency of heterospecific complexes in COS-1 cells. Moreover, the results showed that replication of the viral-like reporter RNA was more efficient when PB2 and NP were both derived from the same avian or human virus or when PB1 was derived from an avian virus, whatever the origin of the other proteins. Furthermore, the PB1 and PB2 proteins from the A/Hong- Kong/156/97 virus exhibited intermediate properties with respect to the corresponding proteins from avian or human influenza viruses, suggesting that some molecular characteristics of PB1 and PB2 proteins might at least partially account for the ability of the A/Hong Kong/156/97 virus to replicate in humans.

scholarly journals Reverse genetics approach towards understanding pathogenesis of H5N1 Hong Kong influenza A virus infection

2001 ◽  
Vol 356 (1416) ◽  
pp. 1841-1843 ◽  
Author(s):  
Masato Hatta ◽  
Gabriele Neumann ◽  
Yoshihiro Kawaoka
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Influenza A ◽  
Reverse Genetics ◽  
Gene Segment ◽  
Influenza Viruses ◽  
H5n1 Influenza ◽  
Influenza A Virus Infection ◽  
Cloned Cdna ◽  
First Time

In 1990, Palese and colleagues established a method (reverse genetics) that allowed one to generate influenza virus containing a gene segment derived from cloned cDNA. Although this method contributed tremendously to our understanding of influenza pathogenesis, the requirement of helper viruses limited its use in many experimental settings. Recently, we and others established systems for the generation of influenza viruses entirely from cloned cDNAs. These systems require only DNA cloning and transfection techniques, and can therefore be easily implemented by laboratories working in the fields of molecular biology and virology. Thus, for the first time, a system is now available that allows highly efficient generation of influenza virus without technical limitations. Using this technology, we generated the same strain of H5N1 influenza viruses that caused an outbreak in Hong Kong in 1997, killing six people.

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