A single amino acid at position 158 in hemagglutinin affects the antigenic property of Eurasian Avian‐like H1N1 Swine influenza viruses

2021 ◽  
Author(s):  
Zeng Wang ◽  
Yan Chen ◽  
Huayuan Chen ◽  
Fei Meng ◽  
Shiyu Tao ◽  
...  
Keyword(s):  
Amino Acid ◽  
Swine Influenza ◽  
Antigenic Property ◽  
Influenza Viruses ◽  
Single Amino Acid

scholarly journals A Single Amino Acid at Position 158 in Hemagglutinin Affects the Antigenic Property of Eurasian Avian-like H1N1 Swine Influenza Viruses

2021 ◽  
Author(s):  
Zeng Wang ◽  
Yan Chen ◽  
Huayuan Chen ◽  
Fei Meng ◽  
Shiyu Tao ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Antigenic Variation ◽  
Swine Influenza ◽  
Antigenic Property ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Single Amino Acid ◽  
Ha Protein

Influenza viruses have been posing a great threat to public health and animal industry. The developed vaccines have been widely used to reduce the risk of potential pandemic; however, the ongoing antigenic drift makes influenza virus escape from host immune response and hampers vaccine efficacy. Until now, the genetic basis of antigenic variation remains largely unknown. In this study, we used A/swine/Guangxi/18/2011 (GX/18) and A/swine/Guangdong/104/2013 (GD/104) as models to explore the molecular determinant for antigenic variation of Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs), and found that the GD/104 virus exhibited 32~64-fold lower antigenic cross-reactivity with antibodies against GX/18 virus. Therefore, we generated polyclonal antibodies against GX/18 or GD/104 virus and a monoclonal antibody (mAb), named mAb102-95, targeted to the hemagglutinin (HA) protein of GX/18 virus, and found that a single amino acid substitution at position 158 in HA protein substantially altered the antigenicity of virus. The reactivity of GX/18 virus containing G158E mutation with the mAb102-95 decreased 8-fold than that of the parental strain. Contrarily, the reactivity of GD/104 virus bearing E158G mutation with the mAb102-95 increased by 32 times as compared with that of the parental virus. Structural analysis showed that the amino acid mutation from G to E was accompanied with the R group changing from -H to -(CH ) -COOH. The induced steric effect and increased hydrophilicity of HA protein surface jointly contributed to the antigenic drift of EA H1N1 SIVs. Our study provides experimental evidence that G158E mutation in HA protein affects the antigenic property of EA H1N1 SIVs, and widens our horizon on the antigenic drift of influenza virus.

scholarly journals Erratum for Xu et al., “A Single Amino Acid at Position 431 of the PB2 Protein Determines the Virulence of H1N1 Swine Influenza Viruses in Mice”

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Chengzhi Xu ◽  
Bangfeng Xu ◽  
Yunpu Wu ◽  
Shiman Yang ◽  
Yunhui Jia ◽  
...  
Keyword(s):  
Amino Acid ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Single Amino Acid

scholarly journals A Single Amino Acid at Position 431 of the PB2 Protein Determines the Virulence of H1N1 Swine Influenza Viruses in Mice

2020 ◽  
Vol 94 (8) ◽  
Author(s):  
Chengzhi Xu ◽  
Bangfeng Xu ◽  
Yunpu Wu ◽  
Shiman Yang ◽  
Yunhui Jia ◽  
...  
Keyword(s):  
Amino Acid ◽  
Genetic Basis ◽  
Critical Role ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Liaoning Province ◽  
Single Amino Acid ◽  
Genetic Determinants ◽  
Viral Virulence ◽  
Swine Population

The frequent reassortment among different influenza viruses in pigs adds complexity to the epidemiology of swine influenza. The diverse viral virulence phenotypes underline the need to investigate the possible genetic determinants for evaluating the pandemic potential to human public health. Here, we found that multiple genotypes of influenza viruses cocirculate in the swine population in Liaoning Province, China. Furthermore, we pinpointed a single amino acid at position 431 in the PB2 protein which plays a critical role in the virulence of H1N1 viruses in mice and found that the alteration of viral polymerase activities is the cause of the different virulence. Our study further indicated that the virulence of influenza virus is a polygenic trait, and the newly identified virulence-related residue in the PB2 provides important information for broadening knowledge on the genetic basis of viral virulence of influenza viruses.

scholarly journals The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 52 ◽  
Author(s):  
Mengkai Cai ◽  
Ruting Zhong ◽  
Chenxiao Qin ◽  
Zhiqing Yu ◽  
Xiaoyan Wen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Genetics ◽  
H1n1 Virus ◽  
Swine Influenza ◽  
Polymerase Activity ◽  
Human Infection ◽  
Influenza Viruses ◽  
Epidemiological Surveillance ◽  
Single Amino Acid ◽  
Swine Industry

The Eurasian avian-like swine (EA) H1N1 virus has affected the Chinese swine industry, and human infection cases have been reported occasionally. However, little is known about the pathogenic mechanism of EA H1N1 virus. In this study, we compared the mouse pathogenicity of A/swine/Guangdong/YJ4/2014 (YJ4) and A/swine/Guangdong/MS285/2017 (MS285) viruses, which had similar genotype to A/Hunan/42443/2015 (HuN-like). None of the mice inoculated with 106 TCID50 of YJ4 survived at 7 days post infection, while the survival rate of the MS285 group was 100%. Therefore, a series of single fragment reassortants in MS285 background and two rescued wild-type viruses were generated by using the reverse genetics method, and the pathogenicity analysis revealed that the PB2 gene contributed to the high virulence of YJ4 virus. Furthermore, there were 11 amino acid differences in PB2 between MS285 and YJ4 identified by sequence alignment, and 11 single amino acid mutant viruses were generated in the MS285 background. We found that the R251K mutation significantly increased the virulence of MS285 in mice, contributed to high polymerase activity and enhanced viral genome transcription and replication. These results indicate that PB2-R251K contributes to the virulence of the EA H1N1 virus and provide new insight into future molecular epidemiological surveillance strategies.

scholarly journals A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Zeng Wang ◽  
Huanliang Yang ◽  
Yan Chen ◽  
Shiyu Tao ◽  
Liling Liu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Glutamic Acid ◽  
Guinea Pigs ◽  
Swine Influenza Virus ◽  
Virus Transmission ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Single Amino Acid ◽  
Efficient Transmission

ABSTRACT Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding.

Variation in the HA antigenicity of A(H1N1)pdm09-related swine influenza viruses

2021 ◽  
Author(s):  
Ahmed Magdy Khalil ◽  
Reiko Yoshida ◽  
Tatsunori Masatani ◽  
Ayato Takada ◽  
Makoto Ozawa
Keyword(s):  
Genetic Diversity ◽  
Amino Acid ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Gene Segment ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Single Amino Acid ◽  
Ha Gene ◽  
The Impact

Since the influenza pandemic in 2009, the causative agent ‘A(H1N1)pdm09 virus’, has been circulating in both human and swine populations. Although phylogenetic analyses of the haemagglutinin (HA) gene segment have revealed broader genetic diversity of A(H1N1)pdm09-related swine influenza A viruses (swIAVs) compared with human A(H1N1)pdm09 viruses, it remains unclear whether the genetic diversity reflects the antigenic differences in HA. To assess the impact of the diversity of the HA gene of A(H1N1)pdm09-related swIAVs on HA antigenicity, we characterized 12 swIAVs isolated in Japan from 2013 to 2018. We used a ferret antiserum and a panel of anti-HA mouse monoclonal antibodies (mAbs) raised against an early A(H1N1)pdm09 isolate. The neutralization assay with the ferret antiserum revealed that five of the 12 swIAVs were significantly different in their HA antigenicity from the early A(H1N1)pdm09 isolate. The mAbs also showed differential neutralization patterns depending on the swIAV strains. In addition, the single amino acid substitution at position 190 of HA, which was found in one of the five antigenically different swIAVs but not in human isolates, was shown to be one of the critical determinants for the antigenic difference of swIAV HAs. Two potential N-glycosylation sites at amino acid positions 185 and 276 of the HA molecule were identified in two antigenically different swIAVs. These results indicated that the genetic diversity of HA in the A(H1N1)pdm09-related swIAVs is associated with their HA antigenic variation. Our findings highlighted the need for surveillance to monitor the emergence of swIAV antigenic variants with public health importance.

scholarly journals A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice

2009 ◽  
Vol 83 (21) ◽  
pp. 11102-11115 ◽  
Author(s):  
Jamie L. Fornek ◽  
Laura Gillim-Ross ◽  
Celia Santos ◽  
Victoria Carter ◽  
Jerrold M. Ward ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Amino Acid ◽  
T Cell ◽  
Amino Acid Substitution ◽  
Systemic Infection ◽  
Influenza Viruses ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
H5n1 Influenza

ABSTRACT The transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid 627 in the PB2 protein exhibited an increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T-cell receptor activation was impaired at 2 days postinfection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not attributable solely to differences in viral replication in the lungs but to an inefficient immune response early in infection as well. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. The disruption of these factors by a single-amino-acid substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites.

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.

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