Special Issue "Host–Pathogen Interactions During Influenza Virus Infection"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 October 2019).

Special Issue Editor

Dr. Richard Sugrue
E-Mail Website
Guest Editor
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
Interests: RNA viruses; host-cell factors; lipid-rafts

Special Issue Information

Dear Colleagues,

Although feral ducks are proposed to be the natural reservoir of influenza A viruses, these viruses are also able to infect a wide variety of mammalian and avian species. However, each type of influenza A virus strain must adapt to its respective host, and this species specificity has led to a high degree of sequence variation within influenza A viruses. Over the past 100 years, there have been several major influenza A virus pandemics that have claimed millions of lives, and high levels of mortality are also associated with annual seasonal influenza A virus infections. In addition to impacts on human health, influenza A virus infection of domestic poultry can also have significant social and economic impacts. In many cases, the influenza A viruses infecting humans has originated in other animals prior to human adaptation. For example, it was previously proposed that avian viruses infect humans through an intermediate mammalian species, which allows the adaptation of the avian virus to a non-avian host. However, direct avian-to-human transmission can also occur, and depending on the virus strain involved, such episodes can be associated with high levels of mortality. Irrespective of the mechanism of transmission, the ability of an influenza A virus strain to” jump the species barrier” requires several adaptive mutations. Furthermore, additional adaptive mutations are required for the maintenance of the virus in its new host. These adaptive mutations can occur in a variety of different virus proteins, including those that form the virus polymerase complex, the virus spike proteins and the virus proteins that play a role in evading the innate immune response. It is presumed that many of these mutations lead to changes in the amino acid sequence of the virus proteins, and that these changes in protein structure promote a proviral state in the cell. These changes may facilitate either the interaction between specific virus proteins and essential host cell factors, or they may activate pro-viral cellular pathways and processes in the new host.

The influenza A virus strain that will give rise to the next global pandemic cannot be predicted. This problem is further exacerbated by the potential for newly emerged influenza virus strains to rapidly circulate around the world. An improved understanding of the biological properties of the viruses that are currently circulating in the natural environment should aid our ability to evaluate the threat that these viruses pose to human and animal health. In addition, this improved understanding should also allow the development of new antiviral strategies to counter the new pandemic strains that will emerge in the future. In this Special Issue, a series of articles have been collated that focus on understanding the interaction between the influenza viruses and the host that they infect.

Dr. Richard Sugrue
Guest Editor

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Keywords

  • avian influenza virus
  • influenza A virus
  • host-cell interactions
  • adaptive mutations
  • seasonal influenza virus
  • influenza virus pandemic

Published Papers (5 papers)

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Research

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Open AccessArticle
RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications
Cells 2019, 8(9), 986; https://doi.org/10.3390/cells8090986 - 27 Aug 2019
Cited by 1
Abstract
The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. [...] Read more.
The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals. Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection. We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections. Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point. In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations. These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management. Full article
(This article belongs to the Special Issue Host–Pathogen Interactions During Influenza Virus Infection)
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Open AccessArticle
Insights into Early Recovery from Influenza Pneumonia by Spatial and Temporal Quantification of Putative Lung Regenerating Cells and by Lung Proteomics
Cells 2019, 8(9), 975; https://doi.org/10.3390/cells8090975 - 26 Aug 2019
Abstract
During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by the influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal [...] Read more.
During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by the influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal distribution is still unknown during influenza-induced acute lung injury. Here, we investigated the distribution of these cells, and concurrently performed global proteomic analysis of the infected lungs to elucidate and link the cellular and molecular events during influenza pneumonia recovery. BALB/c mice were infected with a sub-lethal dose of influenza H1N1 virus. From 5 to 25 days post-infection (dpi), mouse lungs were subjected to histopathologic and immunofluorescence analysis to probe for global distribution of lung repair cells (using P63 and KRT5 markers for DASCs; SPC and PCNA markers for AT2 cells). At 7 and 15 dpi, infected mouse lungs were also subjected to protein mass spectrometry for relative protein quantification. DASCs appeared only in the damaged area of the lung from 7 dpi onwards, reaching a peak at 21 dpi, and persisted until 25 dpi. However, no differentiation of DASCs to AT2 cells was observed by 25 dpi. In contrast, AT2 cells began proliferating from 7 dpi to replenish their population, especially within the boundary area between damaged and undamaged areas of the infected lungs. Mass spectrometry and gene ontology analysis revealed prominent innate immune responses at 7 dpi, which shifted towards adaptive immune responses by 15 dpi. Hence, proliferating AT2 cells but not DASCs contribute to AT2 cell regeneration following transition from innate to adaptive immune responses during the early phase of recovery from influenza pneumonia up to 25 dpi. Full article
(This article belongs to the Special Issue Host–Pathogen Interactions During Influenza Virus Infection)
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Open AccessArticle
Influenza A Hemagglutinin Passage Bias Sites and Host Specificity Mutations
Cells 2019, 8(9), 958; https://doi.org/10.3390/cells8090958 - 22 Aug 2019
Abstract
Animal studies aimed at understanding influenza virus mutations that change host specificity to adapt to replication in mammalian hosts are necessarily limited in sample numbers due to high cost and safety requirements. As a safe, higher-throughput alternative, we explore the possibility of using [...] Read more.
Animal studies aimed at understanding influenza virus mutations that change host specificity to adapt to replication in mammalian hosts are necessarily limited in sample numbers due to high cost and safety requirements. As a safe, higher-throughput alternative, we explore the possibility of using readily available passage bias data obtained mostly from seasonal H1 and H3 influenza strains that were differentially grown in mammalian (MDCK) and avian cells (eggs). Using a statistical approach over 80,000 influenza hemagglutinin sequences with passage information, we found that passage bias sites are most commonly found in three regions: (i) the globular head domain around the receptor binding site, (ii) the region that undergoes pH-dependent structural changes and (iii) the unstructured N-terminal region harbouring the signal peptide. Passage bias sites were consistent among different passage cell types as well as between influenza A subtypes. We also find epistatic interactions of site pairs supporting the notion of host-specific dependency of mutations on virus genomic background. The sites identified from our large-scale sequence analysis substantially overlap with known host adaptation sites in the WHO H5N1 genetic changes inventory suggesting information from passage bias can provide candidate sites for host specificity changes to aid in risk assessment for emerging strains. Full article
(This article belongs to the Special Issue Host–Pathogen Interactions During Influenza Virus Infection)
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Review

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Open AccessReview
Viroporins in the Influenza Virus
Cells 2019, 8(7), 654; https://doi.org/10.3390/cells8070654 - 29 Jun 2019
Cited by 1
Abstract
Influenza is a highly contagious virus that causes seasonal epidemics and unpredictable pandemics. Four influenza virus types have been identified to date: A, B, C and D, with only A–C known to infect humans. Influenza A and B viruses are responsible for seasonal [...] Read more.
Influenza is a highly contagious virus that causes seasonal epidemics and unpredictable pandemics. Four influenza virus types have been identified to date: A, B, C and D, with only A–C known to infect humans. Influenza A and B viruses are responsible for seasonal influenza epidemics in humans and are responsible for up to a billion flu infections annually. The M2 protein is present in all influenza types and belongs to the class of viroporins, i.e., small proteins that form ion channels that increase membrane permeability in virus-infected cells. In influenza A and B, AM2 and BM2 are predominantly proton channels, although they also show some permeability to monovalent cations. By contrast, M2 proteins in influenza C and D, CM2 and DM2, appear to be especially selective for chloride ions, with possibly some permeability to protons. These differences point to different biological roles for M2 in types A and B versus C and D, which is also reflected in their sequences. AM2 is by far the best characterized viroporin, where mechanistic details and rationale of its acid activation, proton selectivity, unidirectionality, and relative low conductance are beginning to be understood. The present review summarizes the biochemical and structural aspects of influenza viroporins and discusses the most relevant aspects of function, inhibition, and interaction with the host. Full article
(This article belongs to the Special Issue Host–Pathogen Interactions During Influenza Virus Infection)
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Open AccessReview
Cellular Proteostasis During Influenza A Virus Infection—Friend or Foe?
Cells 2019, 8(3), 228; https://doi.org/10.3390/cells8030228 - 09 Mar 2019
Cited by 2
Abstract
In order to efficiently replicate, viruses require precise interactions with host components and often hijack the host cellular machinery for their own benefit. Several mechanisms involved in protein synthesis and processing are strongly affected and manipulated by viral infections. A better understanding of [...] Read more.
In order to efficiently replicate, viruses require precise interactions with host components and often hijack the host cellular machinery for their own benefit. Several mechanisms involved in protein synthesis and processing are strongly affected and manipulated by viral infections. A better understanding of the interplay between viruses and their host-cell machinery will likely contribute to the development of novel antiviral strategies. Here, we discuss the current knowledge on the interactions between influenza A virus (IAV), the causative agent for most of the annual respiratory epidemics in humans, and the host cellular proteostasis machinery during infection. We focus on the manipulative capacity of this virus to usurp the cellular protein processing mechanisms and further review the protein quality control mechanisms in the cytosol and in the endoplasmic reticulum that are affected by this virus. Full article
(This article belongs to the Special Issue Host–Pathogen Interactions During Influenza Virus Infection)
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