scholarly journals Amino Acid Substitutions in PB1 of Avian Influenza Viruses Influence Pathogenicity and Transmissibility in Chickens

2014 ◽  
Vol 88 (19) ◽  
pp. 11130-11139 ◽  
Author(s):  
Y. Suzuki ◽  
Y. Uchida ◽  
T. Tanikawa ◽  
N. Maeda ◽  
N. Takemae ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Influenza Viruses ◽  
Amino Acid Substitutions ◽  
Avian Influenza Viruses

scholarly journals Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice

Virology ◽  
2009 ◽  
Vol 384 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Shufang Fan ◽  
Guohua Deng ◽  
Jiasheng Song ◽  
Guobin Tian ◽  
Yongbing Suo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Matrix Protein ◽  
Influenza Viruses ◽  
Amino Acid Residues ◽  
Avian Influenza Viruses ◽  
H5n1 Avian Influenza ◽  
The Matrix ◽  
Matrix Protein M1

scholarly journals Evolution and Adaptation of the Avian H7N9 Virus into the Human Host

2020 ◽  
Vol 8 (5) ◽  
pp. 778
Author(s):  
Andrew T. Bisset ◽  
Gerard F. Hoyne
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Influenza A ◽  
Amino Acid Sequences ◽  
Influenza Viruses ◽  
Amino Acid Substitutions ◽  
Upper Respiratory Tract ◽  
Viral Polymerase ◽  
Evolutionary Changes ◽  
Avian Origin

Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus.

scholarly journals Amino Acid Residue 217 in the Hemagglutinin Glycoprotein Is a Key Mediator of Avian Influenza H7N9 Virus Antigenicity

2018 ◽  
Vol 93 (1) ◽  
Author(s):  
Pengxiang Chang ◽  
Joshua E. Sealy ◽  
Jean-Remy Sadeyen ◽  
Munir Iqbal
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Immune Escape ◽  
Influenza Viruses ◽  
Single Mutation ◽  
H7n9 Virus ◽  
Avian Influenza Viruses ◽  
Antigenic Analysis ◽  
Neutralizing Capacity ◽  
High Pathogenicity

ABSTRACTAvian influenza viruses continue to evolve and acquire mutations that facilitate antigenic drift and virulence change. In 2017, low-pathogenicity H7N9 avian influenza viruses evolved to a high-pathogenicity phenotype in China. Comparative antigenic analysis of the low- and high-pathogenicity virus strains showed marked variability. In order to identify residues that may be linked to the antigenic change among the H7N9 viruses, we serially passaged the viruses in the presence of homologous ferret antiserum. Progeny viruses able to overcome the neutralizing capacity of the antiserum were sequenced. The analysis showed that the emergent immune escape viruses contained mutations A125T, A151T, and L217Q in the hemagglutinin (HA) glycoprotein as early as passage 5 and that these mutations persisted until passage 10. The results revealed that a single mutation, L217Q, in the HA of H7N9 virus led to 23- and 8-fold reductions in hemagglutination inhibition (HI) titer with ferret and chicken antisera, respectively. Further analysis showed that this change also contributed to antigenic differences between the low- and high-pathogenicity H7N9 viruses, thus playing a major role in their antigenic diversification. Therefore, evolutionary changes at amino acid position 217 in the H7N9 viruses can serve as a genetic marker for virus antigenic diversity during vaccine seed matching and selection. Thein vitroimmune escape mutant selection method used in this study could also aid in the prediction of emerging antigenic variants in naturally infected or immunized animals.IMPORTANCEAvian influenza H7N9 viruses circulating in poultry and wild birds continue to evolve and acquire important phenotypic changes. Mutations to the virus hemagglutinin (HA) glycoprotein can modulate virus antigenicity and facilitate virus escape from natural or vaccine-induced immunity. The focus of this study was to identify evolutionary markers in the HA of H7N9 that drive escape from antibody-based immunity. To achieve this, we propagated low-pathogenicity H7N9 virus in the presence of polyclonal antiserum derived from ferrets infected with the same strain of virus (homologous antiserum). This selection process was repeated 10 times. The HA gene sequences of viruses recovered after the fifth passage showed that the viruses readily acquired mutations at three different amino acid positions (A125T, A151T, and L217Q). Further functional analysis of these mutations confirmed that the mutation at residue 217 in the HA was responsible for mediating changes to the immunological properties of the H7N9 virus.

scholarly journals Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X

2015 ◽  
Vol 161 (2) ◽  
pp. 307-316 ◽  
Author(s):  
Takahiro Hiono ◽  
Masatoshi Okamatsu ◽  
Manabu Igarashi ◽  
Ryan McBride ◽  
Robert P. de Vries ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Influenza Viruses ◽  
Sialyl Lewis X ◽  
Amino Acid Residues ◽  
Avian Influenza Viruses ◽  
Lewis X ◽  
Sialyl Lewis

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 Emergence of Highly Pathogenic Avian Influenza A(H5N1) Virus PB1-F2 Variants and Their Virulence in BALB/c Mice

2015 ◽  
Vol 89 (11) ◽  
pp. 5835-5846 ◽  
Author(s):  
Ram P. Kamal ◽  
Amrita Kumar ◽  
Charles T. Davis ◽  
Wen-Pin Tzeng ◽  
Tung Nguyen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Influenza A ◽  
Influenza Viruses ◽  
Full Length ◽  
Start Codon ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Mammalian Infection ◽  
Pathogenic H5n1

ABSTRACTInfluenza A viruses (IAVs) express the PB1-F2 protein from an alternate reading frame within the PB1 gene segment. The roles of PB1-F2 are not well understood but appear to involve modulation of host cell responses. As shown in previous studies, we find that PB1-F2 proteins of mammalian IAVs frequently have premature stop codons that are expected to cause truncations of the protein, whereas avian IAVs usually express a full-length 90-amino-acid PB1-F2. However, in contrast to other avian IAVs, recent isolates of highly pathogenic H5N1 influenza viruses had a high proportion of PB1-F2 truncations (15% since 2010; 61% of isolates in 2013) due to several independent mutations that have persisted and expanded in circulating viruses. One natural H5N1 IAV containing a mutated PB1-F2 start codon (i.e., lacking ATG) was 1,000-fold more virulent for BALB/c mice than a closely related H5N1 containing intact PB1-F2.In vitro, we detected expression of an in-frame protein (C-terminal PB1-F2) from downstream ATGs in PB1-F2 plasmids lacking the well-conserved ATG start codon. Transient expression of full-length PB1-F2, truncated (24-amino-acid) PB1-F2, and PB1-F2 lacking the initiating ATG in mammalian and avian cells had no effect on cell apoptosis or interferon expression in human lung epithelial cells. Full-length and C-terminal PB1-F2 mutants colocalized with mitochondria in A549 cells. Close monitoring of alterations of PB1-F2 and their frequency in contemporary avian H5N1 viruses should continue, as such changes may be markers for mammalian virulence.IMPORTANCEAlthough most avian influenza viruses are harmless for humans, some (such as highly pathogenic H5N1 avian influenza viruses) are capable of infecting humans and causing severe disease with a high mortality rate. A number of risk factors potentially associated with adaptation to mammalian infection have been noted. Here we demonstrate that the protein PB1-F2 is frequently truncated in recent isolates of highly pathogenic H5N1 viruses. Truncation of PB1-F2 has been proposed to act as an adaptation to mammalian infection. We show that some forms of truncation of PB1-F2 may be associated with increased virulence in mammals. Our data support the assessment of PB1-F2 truncations for genomic surveillance of influenza viruses.

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