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 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 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 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 Rapid Evolution of H5N1 Influenza Viruses in Chickens in Hong Kong

1999 ◽  
Vol 73 (4) ◽  
pp. 3366-3374 ◽  
Author(s):  
Nan Nan Zhou ◽  
Kennedy F. Shortridge ◽  
Eric C. J. Claas ◽  
Scott L. Krauss ◽  
Robert G. Webster
Keyword(s):  
Amino Acids ◽  
Hong Kong ◽  
Amino Acid ◽  
Rapid Evolution ◽  
Amino Acid Sequences ◽  
Influenza Viruses ◽  
H5n1 Avian Influenza Virus ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza ◽  
Phylogenetic Lineages

ABSTRACT The H5N1 avian influenza virus that killed 6 of 18 persons infected in Hong Kong in 1997 was transmitted directly from poultry to humans. Viral isolates from this outbreak may provide molecular clues to zoonotic transfer. Here we demonstrate that the H5N1 viruses circulating in poultry comprised two distinguishable phylogenetic lineages in all genes that were in very rapid evolution. When introduced into new hosts, influenza viruses usually undergo rapid alteration of their surface glycoproteins, especially in the hemagglutinin (HA). Surprisingly, these H5N1 isolates had a large proportion of amino acid changes in all gene products except in the HA. These viruses maybe reassortants each of whose HA gene is well adapted to domestic poultry while the rest of the genome arises from a different source. The consensus amino acid sequences of “internal” virion proteins reveal amino acids previously found in human strains. These human-specific amino acids may be important factors in zoonotic transmission.

scholarly journals Characterization of Low-Pathogenic H5 Subtype Influenza Viruses from Eurasia: Implications for the Origin of Highly Pathogenic H5N1 Viruses

2007 ◽  
Vol 81 (14) ◽  
pp. 7529-7539 ◽  
Author(s):  
L. Duan ◽  
L. Campitelli ◽  
X. H. Fan ◽  
Y. H. C. Leung ◽  
D. Vijaykrishna ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Gene Pool ◽  
Migratory Birds ◽  
Southern China ◽  
Phylogenetic Analyses ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Hpai H5n1

ABSTRACT Highly pathogenic avian influenza (HPAI) H5N1 viruses are now endemic in many Asian countries, resulting in repeated outbreaks in poultry and increased cases of human infection. The immediate precursor of these HPAI viruses is believed to be A/goose/Guangdong/1/96 (Gs/GD)-like H5N1 HPAI viruses first detected in Guangdong, China, in 1996. From 2000 onwards, many novel reassortant H5N1 influenza viruses or genotypes have emerged in southern China. However, precursors of the Gs/GD-like viruses and their subsequent reassortants have not been fully determined. Here we characterize low-pathogenic avian influenza (LPAI) H5 subtype viruses isolated from poultry and migratory birds in southern China and Europe from the 1970s to the 2000s. Phylogenetic analyses revealed that Gs/GD-like virus was likely derived from an LPAI H5 virus in migratory birds. However, its variants arose from multiple reassortments between Gs/GD-like virus and viruses from migratory birds or with those Eurasian viruses isolated in the 1970s. It is of note that unlike HPAI H5N1 viruses, those recent LPAI H5 viruses have not become established in aquatic or terrestrial poultry. Phylogenetic analyses revealed the dynamic nature of the influenza virus gene pool in Eurasia with repeated transmissions between the eastern and western extremities of the continent. The data also show reassortment between influenza viruses from domestic and migratory birds in this region that has contributed to the expanded diversity of the influenza virus gene pool among poultry in Eurasia.

CHARACTERIZATION OF H5N1 INFLUENZA VIRUSES ISOLATED FROM MIGRATORY BIRDS IN QINGHAI PROVINCE OF CHINA IN 2006

2007 ◽  
Vol 2 (2) ◽  
pp. e5-e5
Author(s):  
Fumin Lei ◽  
Shuang Tang ◽  
Delong Zhao ◽  
Xiaowei Zhang ◽  
Zheng Kou ◽  
...  
Keyword(s):  
Migratory Birds ◽  
Influenza Viruses ◽  
Qinghai Province ◽  
H5n1 Influenza

scholarly journals The Hemagglutinin Protein of Highly Pathogenic H5N1 Influenza Viruses Overcomes an Early Block in the Replication Cycle To Promote Productive Replication in Macrophages

2012 ◽  
Vol 87 (3) ◽  
pp. 1411-1419 ◽  
Author(s):  
Troy D. Cline ◽  
Erik A. Karlsson ◽  
Bradley J. Seufzer ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Viral Gene ◽  
High Morbidity ◽  
Highly Pathogenic ◽  
Raw264.7 Macrophages ◽  
H5n1 Influenza ◽  
Hpai H5n1 ◽  
Productive Replication

ABSTRACTMacrophages are known to be one of the first lines of defense against influenza virus infection. However, they may also contribute to severe disease caused by the highly pathogenic avian (HPAI) H5N1 influenza viruses. One reason for this may be the ability of certain influenza virus strains to productively replicate in macrophages. However, studies investigating the productive replication of influenza viruses in macrophages have been contradictory, and the results may depend on both the type of macrophages used and the specific viral strain. In this work, we investigated the ability of H1 to H16 viruses to productively replicate in primary murine alveolar macrophages and RAW264.7 macrophages. We show that only a subset of HPAI H5N1 viruses, those that cause high morbidity and mortality in mammals, can productively replicate in macrophages, as measured by the release of newly synthesized virus particles into the cell supernatant. Mechanistically, we found that these H5 strains can overcome a block early in the viral life cycle leading to efficient nuclear entry, viral transcription, translation, and ultimately replication. Studies with reassortant viruses demonstrated that expression of the hemagglutinin gene from an H5N1 virus rescued replication of H1N1 influenza virus in macrophages. This study is the first to characterize H5N1 influenza viruses as the only subtype of influenza virus capable of productive replication in macrophages and establishes the viral gene that is required for this characteristic. The ability to productively replicate in macrophages is unique to H5N1 influenza viruses and may contribute to their increased pathogenesis.

scholarly journals Origin of highly pathogenic H5N1 avian influenza virus in China and genetic characterization of donor and recipient viruses

2007 ◽  
Vol 88 (11) ◽  
pp. 3094-3099 ◽  
Author(s):  
Muhammad Mahmood Mukhtar ◽  
Sahibzada T. Rasool ◽  
Degui Song ◽  
Chengliang Zhu ◽  
Qian Hao ◽  
...  
Keyword(s):  
Avian Influenza ◽  
H5n1 Virus ◽  
Influenza Viruses ◽  
Jiangxi Province ◽  
Highly Pathogenic ◽  
Genetic Characteristics ◽  
H5n1 Avian Influenza Virus ◽  
Ha Gene ◽  
H5n1 Avian Influenza ◽  
Hpai H5n1

Genetic analysis of all eight genes of two Nanchang avian influenza viruses, A/Duck/Nanchang/1681/92 (H3N8-1681) and A/Duck/Nanchang/1904/92 (H7N1-1904), isolated from Jiangxi province, China, in 1992, showed that six internal genes of H3N8-1681 virus and five internal (except NS gene) genes of H7N1-1904 virus were closely similar to A/Goose/Guangdong/1/96 (H5N1) virus, the first highly pathogenic avian influenza (HPAI) virus of subtype H5N1 isolated in Asia. The neuraminidase (NA) gene of Gs/Gd/1/96 had the highest genetic similarity with A/Duck/Hokkaido/55/96 (H1N1-55) virus. The haemagglutinin (HA) gene of Gs/Gd/1/96 virus might have originated as a result of mutation of H5 HA gene from A/Swan/Hokkaido/51/96 (H5N3-51)-like viruses. The PA gene of H5N3-51 virus had the highest similarity with Gs/Gd/1/96. This study explains the origin of first Asian HPAI H5N1 virus in Guangdong by the reassortment of Nanchang (close to Guangdong) and Hokkaido (Japan) (H1N1-55 and H5N3-51) viruses. Genetic characteristics of donor and recipient viruses were also studied.

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 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.

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