scholarly journals Continued Evolution of H5N1 Influenza Viruses in Wild Birds, Domestic Poultry, and Humans in China from 2004 to 2009

2010 ◽  
Vol 84 (17) ◽  
pp. 8389-8397 ◽  
Author(s):  
Yanbing Li ◽  
Jianzhong Shi ◽  
Gongxun Zhong ◽  
Guohua Deng ◽  
Guobin Tian ◽  
...  
Keyword(s):  
Southern China ◽  
Disease Outbreaks ◽  
Northern China ◽  
Wild Birds ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Mild Disease ◽  
H5n1 Influenza ◽  
Domestic Poultry ◽  
H5n1 Avian Influenza

ABSTRACT Despite substantial efforts to control H5N1 avian influenza viruses (AIVs), the viruses have continued to evolve and cause disease outbreaks in poultry and infections in humans. In this report, we analyzed 51 representative H5N1 AIVs isolated from domestic poultry, wild birds, and humans in China during 2004 to 2009, and 21 genotypes were detected based on whole-genome sequences. Twelve genotypes of AIVs in southern China bear similar H5 hemagglutinin (HA) genes (clade 2.3). These AIVs did not display antigenic drift and could be completely protected against by the A/goose/Guangdong/1/96 (GS/GD/1/96)-based oil-adjuvanted killed vaccine and recombinant Newcastle disease virus vaccine, which have been used in China. In addition, antigenically drifted H5N1 viruses, represented by A/chicken/Shanxi/2/06 (CK/SX/2/06), were detected in chickens from several provinces in northern China. The CK/SX/2/06-like viruses are reassortants with newly emerged HA, NA, and PB1 genes that could not be protected against by the GS/GD/1/96-based vaccines. These viruses also reacted poorly with antisera generated from clade 2.2 and 2.3 viruses. The majority of the viruses isolated from southern China were lethal in mice and ducks, while the CK/SX/2/06-like viruses caused mild disease in mice and could not replicate in ducks. Our results demonstrate that the H5N1 AIVs circulating in nature have complex biological characteristics and pose a continued challenge for disease control and pandemic preparedness.

scholarly journals Characterization of Clade 7.2 H5 Avian Influenza Viruses That Continue To Circulate in Chickens in China

2016 ◽  
Vol 90 (21) ◽  
pp. 9797-9805 ◽  
Author(s):  
Liling Liu ◽  
Xianying Zeng ◽  
Pucheng Chen ◽  
Guohua Deng ◽  
Yanbing Li ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Northern China ◽  
Disease Diagnosis ◽  
Influenza Viruses ◽  
Full Genome Sequence ◽  
Avian Influenza Viruses ◽  
Late 20Th Century ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza ◽  
Routine Surveillance

ABSTRACTThe H5N1 avian influenza viruses emerged in Southeast Asia in the late 20th century and have evolved into multiple phylogenetic clades based on their hemagglutinin (HA)-encoding genes. The clade 7.2 viruses were first detected in chickens in northern China in 2006, and vaccines specifically targeted to the clade were developed and have been used in poultry in China since 2006. During routine surveillance and disease diagnosis, we isolated seven H5 viruses between 2011 and 2014 that bear the clade 7.2 HA genes. Here, we performed extensive studies to understand how the clade 7.2 H5 viruses have evolved in chickens in China. Full genome sequence analysis revealed that the seven viruses formed two subtypes (four H5N1 viruses and three H5N2 viruses) and four genotypes by deriving genes from other influenza viruses. All of the viruses had antigenically drifted from the clade 7.2 viruses that were isolated in 2006. Pathogenicity studies of four viruses, one from each genotype, revealed that all of the viruses are highly pathogenic in chickens, but none of them could replicate in ducks. The four viruses exclusively bound to avian-type receptors and replicated only in the turbinates and/or lungs of mice; none of them were lethal to mice at a dosage of 10650% egg infective doses (EID50). Our study indicates that although the clade 7.2 viruses have not been eradicated from poultry through vaccination, they have not become more dangerous to other animals (e.g., ducks and mice) and humans.IMPORTANCEAnimal influenza viruses can acquire the ability to infect and kill humans. The H5N1 viruses have been a concern in recent decades because of their clear pandemic potential. We sorted H5N1 influenza viruses into different phylogenetic clades based on their HA genes. The clade 7.2 viruses were detected in chickens in several provinces of northern China in 2006. Vaccines for these viruses were subsequently developed and have been used ever since to control infection of poultry. Here, we analyzed the genetic and biologic properties of seven clade 7.2 viruses that were isolated from chickens between 2011 and 2014. We found that after nearly 9 years of circulation in chickens, the clade 7.2 viruses still exclusively bind to avian-type receptors and are of low pathogenicity to mice, suggesting that these H5 viruses pose a low risk to human public health.

scholarly journals The nucleoprotein and matrix protein segments of H5N1 influenza viruses are responsible for dominance in embryonated eggs

2011 ◽  
Vol 92 (7) ◽  
pp. 1645-1649 ◽  
Author(s):  
Kenta Shimizu ◽  
Chengjun Li ◽  
Yukiko Muramoto ◽  
Shinya Yamada ◽  
Jiro Arikawa ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Matrix Protein ◽  
Southern China ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza ◽  
M Proteins ◽  
Pathogenic H5n1

Since their emergence in 1996 in southern China, highly pathogenic H5N1 avian influenza viruses have spread widely and continue to circulate in some countries. Genetic reassortment has created multiple H5N1 virus lineages, some of which are dominant in nature. However, the mechanism by which certain H5N1 influenza virus lineages (or genotypes) become dominant in avian species remains unknown. Here, we used competitive inoculation and genetic analysis of the resultant viruses to show that the nucleoprotein (NP) and matrix protein (M) segments of Fujian-like viruses (clade 2.3.4), which became predominant in southern China in mid-2006, are responsible for viral dominance in embryonated eggs. We further found that specific residues in the NP and M proteins play key roles in conferring this viral dominance; specifically, a glutamic acid at position 66 in M2 was conserved among the Fujian-like viruses. These results suggest roles for these viral proteins in influenza virus dominance.

scholarly journals Glycine at Position 622 in PB1 Contributes to the Virulence of H5N1 Avian Influenza Virus in Mice

2015 ◽  
Vol 90 (4) ◽  
pp. 1872-1879 ◽  
Author(s):  
Xiaoxiao Feng ◽  
Zeng Wang ◽  
Jianzhong Shi ◽  
Guohua Deng ◽  
Huihui Kong ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Aspartic Acid ◽  
H5n1 Virus ◽  
Genetic Basis ◽  
Vaccine Development ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Live Attenuated Vaccine ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza

ABSTRACTWe isolated two H5N1 viruses, A/duck/Hunan/S4020/2008 (DK/08) and A/chicken/Guangxi/S2039/2009 (CK/09), from live-bird markets during routine surveillance and found that these two viruses are genetically similar but differ in their replication and virulence in mice. The CK/09 virus is lethal for mice with a 50% mouse lethal dose (MLD50) of 1.6 log1050% egg infectious doses (EID50), whereas the DK/08 virus is nonpathogenic for mice with an MLD50value of 6.2 log10EID50. We explored the genetic basis of the virulence difference of these two viruses by generating a series of reassortant viruses and mutants in the lethal virus CK/09 background and evaluating their virulence in mice. We found that the PB1 gene of the DK/08 virus dramatically attenuated the virulence of the CK/09 virus and that the amino acid at position 622 in PB1 made an important contribution. We further demonstrated that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impaired the binding of PB1 to viral RNA, thereby dramatically decreasing the polymerase activity and attenuating H5N1 virus virulence in mice. Our results identify a novel virulence-related marker of H5N1 influenza viruses and provide a new target for live attenuated vaccine development.IMPORTANCEH5N1 avian influenza viruses have caused the deaths of nearly 60% of the humans that they have infected since 1997 and clearly represent a threat to public health. A thorough understanding of the genetic basis of virulence determinants will provide important insights for antiviral drug and live attenuated vaccine development. Several virulence-related markers in the PB2, PA, M1, and NS1 proteins of H5N1 viruses have been identified. In this study, we isolated two H5N1 avian influenza viruses that are genetically similar but differ in their virulence in mice, and we identified a new virulence-related marker in the PB1 gene. We found that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impairs the binding of PB1 to viral RNA, thereby attenuating H5N1 virus virulence in mice. This newly identified virulence-related marker could be applied to the development of live attenuated vaccines against H5N1 influenza.

scholarly journals Monoclonal Antibody Targeting Neutralizing Epitope on H5N1 Influenza Virus of Clade 1 and 0 for Specific H5 Quantification

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Fang He ◽  
Jimmy Kwang
Keyword(s):  
Monoclonal Antibody ◽  
Mammalian Species ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
H5n1 Influenza Virus ◽  
Neutralizing Epitope ◽  
H5n1 Influenza ◽  
Escape Mutants ◽  
Clade 1 ◽  
Trivalent Vaccine

H5N1 influenza viruses cause high mortality in avian and mammalian species, including humans. Antigenic drift in H5 sequence poses challenges in the development of vaccine and therapeutic antibody. In this study, a monoclonal antibody 11G12 was produced from inactivated H5N1 immunized mice. Results from IFA, ELISA, HI, and virus neutralization indicated that Mab 11G12 can specifically recognize and neutralize H5 type hemagglutinin from clade 1 and 0 without any cross-reaction to any other clades of H5N1 viruses. Mab 11G12 was used to differentiate and quantify the expression of H5N1 strain A/VietNam/1203/04 from a trivalent vaccine mix in ELISA. Sequencing of escape mutants identified that Mab 11G12 targets a major neutralizing epitope of influenza H5 hemagglutinin. The study indicated that some major neutralizing epitopes in H5s of early strains were mutated due to antigenic drift.

Amantadine-resistance among H5N1 avian influenza viruses isolated in Northern China

2008 ◽  
Vol 77 (1) ◽  
pp. 72-76 ◽  
Author(s):  
Guimei He ◽  
Jian Qiao ◽  
Changgui Dong ◽  
Cheng He ◽  
Lihong Zhao ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Northern China ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
H5n1 Avian Influenza ◽  
Amantadine Resistance

scholarly journals Evolutionary Dynamics of Multiple Sublineages of H5N1 Influenza Viruses in Nigeria from 2006 to 2008

2010 ◽  
Vol 84 (7) ◽  
pp. 3239-3247 ◽  
Author(s):  
Alice Fusaro ◽  
Martha I. Nelson ◽  
Tony Joannis ◽  
Luigi Bertolotti ◽  
Isabella Monne ◽  
...  
Keyword(s):  
Evolutionary Dynamics ◽  
Migratory Birds ◽  
Influenza Viruses ◽  
Multiple Introductions ◽  
Poultry Products ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza ◽  
Hpai H5n1 ◽  
Commercial Poultry ◽  
Source Populations

ABSTRACT Highly pathogenic A/H5N1 avian influenza (HPAI H5N1) viruses have seriously affected the Nigerian poultry industry since early 2006. Previous studies have identified multiple introductions of the virus into Nigeria and several reassortment events between cocirculating lineages. To determine the spatial, evolutionary, and population dynamics of the multiple H5N1 lineages cocirculating in Nigeria, we conducted a phylogenetic analysis of whole-genome sequences from 106 HPAI H5N1 viruses isolated between 2006 and 2008 and representing all 25 Nigerian states and the Federal Capital Territory (FCT) reporting outbreaks. We identified a major new subclade in Nigeria that is phylogenetically distinguishable from all previously identified sublineages, as well as two novel reassortment events. A detailed analysis of viral phylogeography identified two major source populations for the HPAI H5N1 virus in Nigeria, one in a major commercial poultry area (southwest region) and one in northern Nigeria, where contact between wild birds and backyard poultry is frequent. These findings suggested that migratory birds from Eastern Europe or Russia may serve an important role in the introduction of HPAI H5N1 viruses into Nigeria, although virus spread through the movement of poultry and poultry products cannot be excluded. Our study provides new insight into the genesis and evolution of H5N1 influenza viruses in Nigeria and has important implications for targeting surveillance efforts to rapidly identify the spread of the virus into and within Nigeria.

scholarly journals A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice

2007 ◽  
Vol 82 (3) ◽  
pp. 1146-1154 ◽  
Author(s):  
Peirong Jiao ◽  
Guobin Tian ◽  
Yanbing Li ◽  
Guohua Deng ◽  
Yongping Jiang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Host Cell ◽  
Amino Acid Substitution ◽  
Influenza Viruses ◽  
Single Amino Acid ◽  
Ns1 Protein ◽  
Avian Influenza Viruses ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza

ABSTRACT In this study, we explored the molecular basis determining the virulence of H5N1 avian influenza viruses in mammalian hosts by comparing two viruses, A/Duck/Guangxi/12/03 (DK/12) and A/Duck/Guangxi/27/03 (DK/27), which are genetically similar but differ in their pathogenicities in mice. To assess the genetic basis for this difference in virulence, we used reverse genetics to generate a series of reassortants and mutants of these two viruses. We found that a single-amino-acid substitution of serine for proline at position 42 (P42S) in the NS1 protein dramatically increased the virulence of the DK/12 virus in mice, whereas the substitution of proline for serine at the same position (S42P) completely attenuated the DK/27 virus. We further demonstrated that the amino acid S42 of NS1 is critical for the H5N1 influenza virus to antagonize host cell interferon induction and for the NS1 protein to prevent the double-stranded RNA-mediated activation of the NF-κB pathway and the IRF-3 pathway. Our results indicate that the NS1 protein is critical for the pathogenicity of H5N1 influenza viruses in mammalian hosts and that the amino acid S42 of NS1 plays a key role in undermining the antiviral immune response of the host cell.

scholarly journals Complete Genomic Sequence of an H5N1 Influenza Virus from a Parrot in Southern China

2012 ◽  
Vol 86 (16) ◽  
pp. 8894-8895 ◽  
Author(s):  
Peirong Jiao ◽  
Yafen Song ◽  
Runyu Yuan ◽  
Liangmeng Wei ◽  
Lan Cao ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Genomic Sequence ◽  
Southern China ◽  
H5n1 Avian Influenza Virus ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza ◽  
Eurasian Lineage ◽  
Complete Genomic

An H5N1 avian influenza virus (AIV) designated A/Parrot/Guangdong/C99/2005 (H5N1) was first isolated from a sick parrot in Guangdong in southern China in 2005. The complete genome of this strain was analyzed. Genome sequence analysis showed that all 8 gene segments of the virus nucleotide had 99.0% homology to A/chicken/Henan/12/2004 (H5N1). Phylogenetic analysis demonstrated that all 8 gene segments of the virus were derived from the Eurasian lineage. The availability of genome sequences is useful to investigate the host range and genetic evolution of the H5N1 avian influenza virus in Southern China.

scholarly journals Molecular analysis of avian H7 influenza viruses circulating in Eurasia in 1999–2005: detection of multiple reassortant virus genotypes

2008 ◽  
Vol 89 (1) ◽  
pp. 48-59 ◽  
Author(s):  
Laura Campitelli ◽  
Angela Di Martino ◽  
Domenico Spagnolo ◽  
Gavin J. D. Smith ◽  
Livia Di Trani ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Southern China ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Phylogenetic Groups ◽  
Entire Genome ◽  
Domestic Poultry ◽  
Virus Genotypes ◽  
In The Wild ◽  
Human Infections

Avian influenza infections by high and low pathogenicity H7 influenza viruses have caused several outbreaks in European poultry in recent years, also resulting in human infections. Although in some cases the source of H7 strains from domestic poultry was shown to be the viruses circulating in the wild bird reservoir, a thorough characterization of the entire genome of H7 viruses from both wild and domestic Eurasian birds, and their evolutionary relationships, has not been conducted. In our study, we have analysed low pathogenicity H7 influenza strains isolated from wild and domestic ducks in Italy and southern China and compared them with those from reared terrestrial poultry such as chicken and turkey. Phylogenetic analysis demonstrated that the H7 haemagglutinin genes were all closely related to each other, whereas the remaining genes could be divided into two or more phylogenetic groups. Almost each year different H7 reassortant viruses were identified and in at least two different years more than one H7 genotype co-circulated. A recent precursor in wild waterfowl was identified for most of the gene segments of terrestrial poultry viruses. Our data suggest that reassortment allows avian influenza viruses, in their natural reservoir, to increase their genetic diversity. In turn this might help avian influenza viruses colonize a wider range of hosts, including domestic poultry.

scholarly journals Comparative Virological and Pathogenic Characteristics of Avian Influenza H5N8 Viruses Detected in Wild Birds and Domestic Poultry in Egypt during the Winter of 2016/2017

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 990 ◽  
Author(s):  
Yassmin Moatasim ◽  
Ahmed Kandeil ◽  
Basma Emad Aboulhoda ◽  
Rabeh El-Shesheny ◽  
Maha Alkhazindar ◽  
...  
Keyword(s):  
Avian Influenza ◽  
A549 Cells ◽  
Wild Birds ◽  
Influenza Viruses ◽  
Multiple Introductions ◽  
Domestic Poultry ◽  
Growth Properties ◽  
Reassortant Viruses

The surveillance and virological characterization of H5N8 avian influenza viruses are important in order to assess their zoonotic potential. The genetic analyses of the Egyptian H5N8 viruses isolated through active surveillance in wild birds and domestic poultry in the winter of 2016/2017 showed multiple introductions of reassortant viruses. In this study, we investigated and compared the growth kinetics, infectivity, and pathogenicity of the three reassortant forms of H5N8 viruses detected in wild birds and domestic poultry in Egypt during the first introduction wave in the winter of 2016/2017. Three representative H5N8 viruses (abbreviated as 813, 871, and 13666) were selected. The 871/H5N8 virus showed enhanced growth properties in vitro in Madin Darby canine kidney (MDCK) and A549 cells. Interestingly, all viruses replicated well in mice without prior adaptation. Infected C57BL/6 mice showed 20% mortality for 813/H5N8 and 60% mortality for 871/H5N8 and 13666/H5N8, which could be attributed to the genetic differences among the viruses. Studies on the pathogenicity in experimentally infected ducks revealed a range of pathogenic effects, with mortality rate ranging from 0% for 813/H5N8 and 13666/H5N8 to 28% for 871/H5N8. No significant differences were observed among the three compared viruses in infected chickens. Overall, different H5N8 viruses had variable biological characteristics, indicating a continuous need for surveillance and virus characterization efforts.

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