RETRACTED: The NS1 gene of H5N1 influenza viruses circumvents the host anti-viral cytokine responses

2004 ◽  
Vol 103 (1-2) ◽  
pp. 107-113 ◽  
Author(s):  
Sang Heui Seo ◽  
Erich Hoffmann ◽  
Robert G Webster
Keyword(s):  
Influenza Viruses ◽  
H5n1 Influenza ◽  
Cytokine Responses ◽  
Ns1 Gene

scholarly journals Addendum: Editorial note: Lethal H5N1 influenza viruses escape host antiviral cytokine responses

2012 ◽  
Vol 18 (10) ◽  
pp. 1592-1592
Author(s):  
Sang Heui Seo ◽  
Erich Hoffmann ◽  
Robert G Webster
Keyword(s):  
Influenza Viruses ◽  
Editorial Note ◽  
H5n1 Influenza ◽  
Cytokine Responses

scholarly journals The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses

2006 ◽  
Vol 80 (22) ◽  
pp. 11115-11123 ◽  
Author(s):  
Zejun Li ◽  
Yongping Jiang ◽  
Peirong Jiao ◽  
Aiqin Wang ◽  
Fengju Zhao ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Recombinant Virus ◽  
Influenza Viruses ◽  
Single Amino Acid ◽  
Amino Acid Difference ◽  
Ns1 Protein ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Ns1 Gene

ABSTRACT In the present study, we explored the genetic basis underlying the virulence and host range of two H5N1 influenza viruses in chickens. A/goose/Guangdong/1/96 (GS/GD/1/96) is a highly pathogenic virus for chickens, whereas A/goose/Guangdong/2/96 (GS/GD/2/96) is unable to replicate in chickens. These two H5N1 viruses differ in sequence by only five amino acids mapping to the PA, NP, M1, and NS1 genes. We used reverse genetics to create four single-gene recombinants that contained one of the sequence-differing genes from nonpathogenic GS/GD/2/96 and the remaining seven gene segments from highly pathogenic GS/GD/1/96. We determined that the NS1 gene of GS/GD/2/96 inhibited the replication of GS/GD/1/96 in chickens, while the substitution of the PA, NP, or M gene did not change the highly pathogenic properties of GS/GD/1/96. Conversely, of the recombinant viruses generated in the GS/GD/2/96 background, only the virus containing the NS1 gene of GS/GD/1/96 was able to replicate and cause disease and death in chickens. The single-amino-acid difference in the sequence of these two NS1 genes resides at position 149. We demonstrate that a recombinant virus expressing the GS/GD/1/96 NS1 protein with Ala149 is able to antagonize the induction of interferon protein levels in chicken embryo fibroblasts (CEFs), but a recombinant virus carrying a Val149 substitution is not capable of the same effect. These results indicate that the NS1 gene is critical for the pathogenicity of avian influenza virus in chickens and that the amino acid residue Ala149 correlates with the ability of these viruses to antagonize interferon induction in CEFs.

Lethal H5N1 influenza viruses escape host anti-viral cytokine responses

10.1038/nm757 ◽  
2002 ◽  
Vol 8 (9) ◽  
pp. 950-954 ◽  
Author(s):  
Sang Heui Seo ◽  
Erich Hoffmann ◽  
Robert G. Webster
Keyword(s):  
Influenza Viruses ◽  
H5n1 Influenza ◽  
Cytokine Responses

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 H5N1 influenza viruses: outbreaks and biological properties

Cell Research ◽  
2009 ◽  
Vol 20 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Gabriele Neumann ◽  
Hualan Chen ◽  
George F Gao ◽  
Yuelong Shu ◽  
Yoshihiro Kawaoka
Keyword(s):  
Biological Properties ◽  
Influenza Viruses ◽  
H5n1 Influenza

scholarly journals Mutations in the PA Protein of Avian H5N1 Influenza Viruses Affect Polymerase Activity and Mouse Virulence

2017 ◽  
pp. JVI.01557-17 ◽  
Author(s):  
Gongxun Zhong ◽  
Mai Quynh Le ◽  
Tiago J.S. Lopes ◽  
Peter Halfmann ◽  
Masato Hatta ◽  
...  
Keyword(s):  
Amino Acid ◽  
Case Fatality ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Viral Polymerase ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Increased Risk ◽  
Severe Infections ◽  
Viral Determinants

To study the influenza viral determinants of pathogenicity, we characterized two highly pathogenic avian H5N1 influenza viruses isolated in Vietnam in 2012 (A/duck/Vietnam/QT1480/2012; QT1480) and 2013 (A/duck/Vietnam/QT1728/2013; QT1728) and found that the activity of their polymerase complexes differed significantly, even though both viruses were highly pathogenic in mice. Further studies revealed that the PA-S343A/E347D mutations reduced viral polymerase activity and mouse virulence when tested in the genetic background of QT1728 virus. In contrast, the PA-343S/347E mutations increased the polymerase activity of QT1480 and the virulence of a low pathogenic H5N1 influenza virus. The PA-343S residue (which alone increased viral polymerase activity and mouse virulence significantly relative to viral replication complexes encoding PA-343A) is frequently found in H5N1 influenza viruses of several subclades; infection with a virus possessing this amino acid may pose an increased risk to humans.IMPORTANCEH5N1 influenza viruses cause severe infections in humans with a case fatality rate that exceeds 50%. The factors that determine the high virulence of these viruses in humans are not fully understood. Here, we identified two amino acid changes in the viral polymerase PA protein that affect the activity of the viral polymerase complex and virulence in mice. Infection with viruses possessing these amino acid changes may pose an increased risk to humans.

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