Molecular Mechanism of the Host Range and Virulence of Influenza Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 14800

Special Issue Editor


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Guest Editor
National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Interests: molecular basis of the virulence of AIV; new vaccines of AIV; evolution of AIV; pathogenesis and immunology of AIV; virus protein and host interaction; genomic-wide CRISPR screening

Special Issue Information

Dear Colleagues,

During the past several decades, avian influenza viruses have become endemic among poultry and wild birds across the globe. It is striking that avian influenza virus continuously crosses the species barrier to infect humans and mammals, posing serious public health issues. To achieve cross-species transmission (known as “host jump”), influenza viruses must change their tropism, evolving rapidly to target new host species, which influences the phenotype of influenza virus in different species. A well-known mammalian adaptive mutation of E627K and A588V in PB2 protein has been reported. However, other molecular bases of influenza virus are also critical when it comes to influencing the adaption of influenza virus in birds and mammals. Therefore, understanding the new molecular basis of host range and virulence of influenza virus is urgently needed.

For this Special Issue on influenza viruses entitled “Molecular Mechanism of the Host Range and Virulence of Influenza Viruses”, we invite you to submit original research, reviews, and perspectives focusing on the molecular mechanisms of influenza viruses.

Prof. Dr. Wenbao Qi
Guest Editor

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Keywords

  • virus evolution
  • influenza virus
  • virulence
  • host range
  • transmission
  • adaption
  • viral replication
  • host species
  • emerging infectious diseases

Published Papers (5 papers)

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Research

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12 pages, 3426 KiB  
Article
Identification of Critical Genes and Pathways for Influenza A Virus Infections via Bioinformatics Analysis
by Gao Chen, Haoyue Li, Mingzhao Hao, Xiaolei Li, Yizhi Dong, Yue Zhang, Xiping Liu, Cheng Lu and Jing Zhao
Viruses 2022, 14(8), 1625; https://doi.org/10.3390/v14081625 - 26 Jul 2022
Cited by 3 | Viewed by 2019
Abstract
Influenza A virus (IAV) requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system but also provides further targets for [...] Read more.
Influenza A virus (IAV) requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system but also provides further targets for antiviral drug development. To uncover critical pathways and potential targets of influenza infection, we assembled a large amount of data from 8 RNA sequencing studies of IAV infection for integrative network analysis. Weighted gene co-expression network analysis (WGCNA) was performed to investigate modules and genes correlated with the time course of infection and/or multiplicity of infection (MOI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and pathways of the genes in 5 significant modules. Top hub genes were identified using the cytoHubba plugin in the protein interaction network. The correlation between expression levels of 7 top hub genes and time course or MOI was displayed and validated, including BCL2L13, PLSCR1, ARID5A, LMO2, NDRG4, HAP1, and CARD10. Dysregulated expression of these genes potently impacted the development of IAV infection through modulating IAV-related biological processes and pathways. This study provides further insights into the underlying molecular mechanisms and potential targets in IAV infection. Full article
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13 pages, 2579 KiB  
Article
Effect of the Interaction between Viral PB2 and Host SphK1 on H9N2 AIV Replication in Mammals
by Yong Zhou, Weihua Gao, Yan Sun, Yuxin Guo, Yuping Wu and Juan Pu
Viruses 2022, 14(7), 1585; https://doi.org/10.3390/v14071585 - 21 Jul 2022
Cited by 5 | Viewed by 2583
Abstract
The H9N2 avian influenza virus (AIV) is currently widespread worldwide, posing a severe threat to the poultry industry and public health. Reassortment is an important way for influenza viruses to adapt to a new host. In 2007, the PB2 gene of H9N2 AIV [...] Read more.
The H9N2 avian influenza virus (AIV) is currently widespread worldwide, posing a severe threat to the poultry industry and public health. Reassortment is an important way for influenza viruses to adapt to a new host. In 2007, the PB2 gene of H9N2 AIV in China was reassorted, and the DK1-like lineage replaced the F/98-like lineage, forming a dominant genotype of G57. This genotype and its reassortants (such as H7N9, H10N8 and H5N6) showed higher mammalian adaptation, and caused increased human infections. However, the adaptive mechanisms of the DK1-like lineage PB2 gene remain unclear. Here, we confirmed that the PB2 lineage of the H9N2 AIV currently prevalent in China still belongs to the DK1-like lineage and, compared with the previously predominant F/98-like lineage, the DK1-like lineage PB2 gene significantly enhances H9N2 AIV to mammalian adaptation. Through transcriptomic analysis and qRT–PCR and western blot experiments, we identified a host factor, sphingosine kinase 1 (SphK1), that is closely related to viral replication. SphK1 inhibits the replication of DK1-like PB2 gene H9N2 AIV, but the ability of SphK1 protein to bind DK1-like PB2 protein is weaker than that of F/98-like PB2 protein, which may contribute to H9N2 AIV containing the DK1-like PB2 gene to escape the inhibitory effect of host factor SphK1 for efficient infection. This study broadens our understanding of the adaptive evolution of H9N2 AIV and highlights the necessity to pay close attention to the AIV that contains the adaptive PB2 protein in animals and humans. Full article
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17 pages, 3616 KiB  
Article
The Genomic Evolution and the Transmission Dynamics of H6N2 Avian Influenza A Viruses in Southern China
by Zhaoxia Yuan, Taifang Zhou, Jiahao Zhang, Qingxin Zeng, Danli Jiang, Meifang Wei and Xudong Li
Viruses 2022, 14(6), 1154; https://doi.org/10.3390/v14061154 - 26 May 2022
Cited by 5 | Viewed by 2124
Abstract
In China, the broad prevalence of H6 subtype influenza viruses, increasingly detected in aquatic birds, promotes their exchange materials with other highly pathogenic human-infecting H5N1, H5N6, and H7N9 influenza viruses. Strikingly, some H6 subtype viruses can infect pigs, dogs, and humans, posing risks [...] Read more.
In China, the broad prevalence of H6 subtype influenza viruses, increasingly detected in aquatic birds, promotes their exchange materials with other highly pathogenic human-infecting H5N1, H5N6, and H7N9 influenza viruses. Strikingly, some H6 subtype viruses can infect pigs, dogs, and humans, posing risks to public health. In this study, 9 H6N2 viruses recovered from waterfowl species in the Guangdong province of China in 2018 were isolated and sequenced. Phylogenetic analysis revealed that the genome sequences of these H6N2 viruses belonged to Group I, except for the NP gene in Group III. Coalescent analyses demonstrated that the reassortment of NA and NS genes have occurred in two independent clusters, suggesting H6 subtype viruses had been undergoing a complex reassortant. To examine the evolutionary dynamics and the dissemination of the H6 subtype viruses, a Bayesian stochastic search variable selection was performed for results showing higher viral migration rates between closer provinces, including Guangdong, Jiangxi, Guangxi, and Fujian. Notably, the transmission routes of the H6 subtype viruses were concentrated in Jiangxi Province, the most frequent location for input and output transmission and a region containing Poyang Lake, a well-known wintering site for migration birds. We also found that the aquatic birds, especially ducks, were the most common input source of the viral transmission. In addition, we also found that eight positively selected amino acid sites were identified in HA protein. Given their continuous dissemination and the broad prevalence of the H6 subtype influenza viruses, continued surveillance is warranted in the future. Full article
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13 pages, 3867 KiB  
Article
Hemagglutinin Gene Variation Rate of H9N2 Avian Influenza Virus by Vaccine Intervention in China
by Ying Cao, Haizhou Liu, Di Liu, Wenjun Liu, Tingrong Luo and Jing Li
Viruses 2022, 14(5), 1043; https://doi.org/10.3390/v14051043 - 13 May 2022
Cited by 6 | Viewed by 2414
Abstract
H9N2 subtype avian influenza virus (AIV) is widespread globally, with China being the main epidemic center. Inactivated virus vaccination was adopted as the main prevention method in China. In this study, 22 hemagglutinin (HA) sequences were obtained from all inactivated vaccine [...] Read more.
H9N2 subtype avian influenza virus (AIV) is widespread globally, with China being the main epidemic center. Inactivated virus vaccination was adopted as the main prevention method in China. In this study, 22 hemagglutinin (HA) sequences were obtained from all inactivated vaccine strains of H9N2 subtype AIVs in China since its introduction. A phylogenetic analysis of the vaccine sequences and HA sequences of all published H9N2 subtype AIVs was conducted to investigate the relationship between vaccine use and the virus genetic diversity of the virus. We found that during 2002–2006, when fewer vaccines were used, annual genetic differences between the HA sequences were mainly distributed between 0.025 and 0.075 and were mainly caused by point mutations. From 2009 to 2013, more vaccines were used, and the genetic distance between sequences was about 10 times greater than between 2002 and 2006, especially in 2013. In addition to the accumulation of point mutations, insertion mutations may be the main reason for the large genetic differences between sequences from 2009 to 2013. These findings suggest that the use of inactivated vaccines affected point mutations in the HA sequences and that the contribution of high-frequency replacement vaccine strains to the rate of virus evolution is greater than that of low-frequency replacement vaccine strains. The selection pressure of the vaccine antibody plays a certain role in regulating the variation of HA sequences in H9N2 subtype AIV. Full article
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Review

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15 pages, 1324 KiB  
Review
Influence of Host Sialic Acid Receptors Structure on the Host Specificity of Influenza Viruses
by Chuankuo Zhao and Juan Pu
Viruses 2022, 14(10), 2141; https://doi.org/10.3390/v14102141 - 28 Sep 2022
Cited by 16 | Viewed by 5126
Abstract
Influenza viruses need to use sialic acid receptors to invade host cells, and the α-2,3 and α-2,6 sialic acids glycosidic bonds linking the terminal sialic acids are generally considered to be the most important factors influencing the cross-species transmission of the influenza viruses. [...] Read more.
Influenza viruses need to use sialic acid receptors to invade host cells, and the α-2,3 and α-2,6 sialic acids glycosidic bonds linking the terminal sialic acids are generally considered to be the most important factors influencing the cross-species transmission of the influenza viruses. The development of methods to detect the binding of influenza virus HA proteins to sialic acid receptors, as well as the development of glycobiological techniques, has led to a richer understanding of the structure of the sialylated glycan in influenza virus hosts. It was found that, in addition to the sialic acid glycosidic bond, sialic acid variants, length of the sialylated glycan, Gal-GlcNAc-linked glycosidic bond within the sialylated glycan, and sulfation/fucosylation of the GlcNAc within the sialylated glycan all affect the binding properties of influenza viruses to the sialic acid receptors, thus indirectly affecting the host specificity of influenza viruses. This paper will review the sialic acid variants, internal structural differences of sialylated glycan molecules that affect the host specificity of influenza viruses, and distribution characteristics of sialic acid receptors in influenza virus hosts, in order to provide a more reliable theoretical basis for the in-depth investigation of cross-species transmission of influenza viruses and the development of new antiviral drugs. Full article
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