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Trends in Microbiology Sep 2018This infographic briefly summarises the natural history, replication cycle, and pathogenesis of influenza viruses, the cause of seasonal influenza and of influenza...
This infographic briefly summarises the natural history, replication cycle, and pathogenesis of influenza viruses, the cause of seasonal influenza and of influenza pandemics. Influenza viruses infect many vertebrates, with Influenza A, B and C viruses (IAV, IBV, and ICV) infecting humans. High mutation rates allow the evasion of immunity. IAV from different host species can 'reassort' their segmented genomes, producing pandemic strains that are antigenically novel but otherwise well adapted to humans. The 'Great Influenza' pandemic of 1918 remains the worst outbreak of infectious disease in history. There is concern that highly pathogenic avian influenza viruses of the H5 and H7 subtypes may evolve to cause similar pandemics. In humans, influenza viruses infect the respiratory epithelium. The haemagglutinin (HA) proteins of IAV and IBV, or the haemagglutinin-esterase-fusion (HEF) proteins of ICV, bind sialic acid, causing endocytosis. Unusually among RNA viruses, the viral genome replicates in the nucleus. New viruses assemble at the cell surface and are released by the receptor-cleaving neuraminidase (NA) proteins of IAV and IBV or the ICV HEF protein.
Topics: Adaptation, Biological; Animals; Coinfection; Disease Outbreaks; Genome, Viral; Host Specificity; Humans; Influenza Vaccines; Orthomyxoviridae; Orthomyxoviridae Infections; Virus Replication
PubMed: 29909041
DOI: 10.1016/j.tim.2018.05.013 -
Cold Spring Harbor Perspectives in... Aug 2020Hemagglutinin (HA) is most abundant glycoprotein on the influenza virus surface. Influenza HA promotes viral entry by engaging the receptor and mediating virus-host... (Review)
Review
Hemagglutinin (HA) is most abundant glycoprotein on the influenza virus surface. Influenza HA promotes viral entry by engaging the receptor and mediating virus-host membrane fusion. At the same time, HA is the major antigen of the influenza virus. HA antigenic shift can result in pandemics, whereas antigenic drift allows human circulating strains to escape herd immunity. Most antibody responses against HA are strain-specific. However, antibodies that have neutralizing activities against multiple strains or even subtypes have now been discovered and characterized. These broadly neutralizing antibodies (bnAbs) target conserved regions on HA, such as the receptor-binding site and the stem domain. Structural studies of such bnAbs have provided important insight into universal influenza vaccine and therapeutic design. This review discusses the HA functions as well as HA-antibody interactions from a structural perspective.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza Vaccines; Influenza, Human; Orthomyxoviridae; Orthomyxoviridae Infections
PubMed: 31871236
DOI: 10.1101/cshperspect.a038778 -
Virulence Dec 2023Influenza viruses, including four major types (A, B, C, and D), can cause mild-to-severe and lethal diseases in humans and animals. Influenza viruses evolve rapidly... (Review)
Review
Influenza viruses, including four major types (A, B, C, and D), can cause mild-to-severe and lethal diseases in humans and animals. Influenza viruses evolve rapidly through antigenic drift (mutation) and shift (reassortment of the segmented viral genome). New variants, strains, and subtypes have emerged frequently, causing epidemic, zoonotic, and pandemic infections, despite currently available vaccines and antiviral drugs. In recent years, avian influenza viruses, such as H5 and H7 subtypes, have caused hundreds to thousands of zoonotic infections in humans with high case fatality rates. The likelihood of these animal influenza viruses acquiring airborne transmission in humans through viral evolution poses great concern for the next pandemic. Severe influenza viral disease is caused by both direct viral cytopathic effects and exacerbated host immune response against high viral loads. Studies have identified various mutations in viral genes that increase viral replication and transmission, alter tissue tropism or species specificity, and evade antivirals or pre-existing immunity. Significant progress has also been made in identifying and characterizing the host components that mediate antiviral responses, pro-viral functions, or immunopathogenesis following influenza viral infections. This review summarizes the current knowledge on viral determinants of influenza virulence and pathogenicity, protective and immunopathogenic aspects of host innate and adaptive immune responses, and antiviral and pro-viral roles of host factors and cellular signalling pathways. Understanding the molecular mechanisms of viral virulence factors and virus-host interactions is critical for the development of preventive and therapeutic measures against influenza diseases.
Topics: Humans; Animals; Influenza, Human; Virulence; Orthomyxoviridae Infections; Influenza A virus; Orthomyxoviridae; Influenza Vaccines; Antiviral Agents; Virus Replication; Influenza in Birds
PubMed: 37339323
DOI: 10.1080/21505594.2023.2223057 -
Nature Reviews. Microbiology Aug 2016The genomes of influenza viruses consist of multiple segments of single-stranded negative-sense RNA. Each of these segments is bound by the heterotrimeric viral... (Review)
Review
The genomes of influenza viruses consist of multiple segments of single-stranded negative-sense RNA. Each of these segments is bound by the heterotrimeric viral RNA-dependent RNA polymerase and multiple copies of nucleoprotein, which form viral ribonucleoprotein (vRNP) complexes. It is in the context of these vRNPs that the viral RNA polymerase carries out transcription of viral genes and replication of the viral RNA genome. In this Review, we discuss our current knowledge of the structure of the influenza virus RNA polymerase, and insights that have been gained into the molecular mechanisms of viral transcription and replication, and their regulation by viral and host factors. Furthermore, we discuss how advances in our understanding of the structure and function of polymerases could help in identifying new antiviral targets.
Topics: Genome, Viral; Host-Pathogen Interactions; Humans; Influenza A virus; Influenza B virus; Models, Molecular; Orthomyxoviridae; Protein Conformation; RNA, Viral; RNA-Dependent RNA Polymerase; Ribonucleoproteins; Viral Proteins; Virion; Virus Replication
PubMed: 27396566
DOI: 10.1038/nrmicro.2016.87 -
Viruses Jul 2021Influenza viruses are still a serious threat to human health. Cytokines are essential for cell-to-cell communication and viral clearance in the immune system, but... (Review)
Review
Influenza viruses are still a serious threat to human health. Cytokines are essential for cell-to-cell communication and viral clearance in the immune system, but excessive cytokines can cause serious immune pathology. Deaths caused by severe influenza are usually related to cytokine storms. The recent literature has described the mechanism behind the cytokine-storm network and how it can exacerbate host pathological damage. Biological factors such as sex, age, and obesity may cause biological differences between different individuals, which affects cytokine storms induced by the influenza virus. In this review, we summarize the mechanism behind influenza virus cytokine storms and the differences in cytokine storms of different ages and sexes, and in obesity.
Topics: Age Factors; Cytokine Release Syndrome; Cytokines; Humans; Immunity, Innate; Influenza, Human; Obesity; Orthomyxoviridae; Sex Factors
PubMed: 34372568
DOI: 10.3390/v13071362 -
Viruses Aug 2018Influenza remains a persistent public health challenge, because the rapid evolution of influenza viruses has led to marginal vaccine efficacy, antiviral resistance, and... (Review)
Review
Influenza remains a persistent public health challenge, because the rapid evolution of influenza viruses has led to marginal vaccine efficacy, antiviral resistance, and the annual emergence of novel strains. This evolvability is driven, in part, by the virus's capacity to generate diversity through mutation and reassortment. Because many new traits require multiple mutations and mutations are frequently combined by reassortment, epistatic interactions between mutations play an important role in influenza virus evolution. While mutation and epistasis are fundamental to the adaptability of influenza viruses, they also constrain the evolutionary process in important ways. Here, we review recent work on mutational effects and epistasis in influenza viruses.
Topics: Animals; Epistasis, Genetic; Evolution, Molecular; Genetic Fitness; Genome, Viral; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza, Human; Mutation; Orthomyxoviridae; Reassortant Viruses
PubMed: 30081492
DOI: 10.3390/v10080407 -
Cold Spring Harbor Perspectives in... Jan 2022Horses are the third major mammalian species, along with humans and swine, long known to be subject to acute upper respiratory disease from influenza A virus infection.... (Review)
Review
Horses are the third major mammalian species, along with humans and swine, long known to be subject to acute upper respiratory disease from influenza A virus infection. The viruses responsible are subtype H7N7, which is believed extinct, and H3N8, which circulates worldwide. The equine influenza lineages are clearly divergent from avian influenza lineages of the same subtypes. Their genetic evolution and potential for interspecies transmission, as well as clinical features and epidemiology, are discussed. Equine influenza is spread internationally and vaccination is central to control efforts. The current mechanism of international surveillance and virus strain recommendations for vaccines is described.
Topics: Animals; Horses; Humans; Influenza A Virus, H3N8 Subtype; Influenza A Virus, H7N7 Subtype; Influenza A virus; Influenza, Human; Orthomyxoviridae Infections; Swine
PubMed: 32152243
DOI: 10.1101/cshperspect.a038331 -
Cell Research Jan 2015Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle...
Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression, but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and rescued viral infection-induced mouse weight loss, but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection.
Topics: Animals; Gene Expression Regulation, Viral; HEK293 Cells; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza A virus; Influenza, Human; Lonicera; Mice; MicroRNAs; Mutation; Orthomyxoviridae Infections; RNA, Plant; Virus Replication
PubMed: 25287280
DOI: 10.1038/cr.2014.130 -
Virulence Dec 2019Virus infection induces different cellular responses in infected cells. These include cellular stress responses like autophagy and unfolded protein response (UPR). Both... (Review)
Review
Virus infection induces different cellular responses in infected cells. These include cellular stress responses like autophagy and unfolded protein response (UPR). Both autophagy and UPR are connected to programed cell death I (apoptosis) in chronic stress conditions to regulate cellular homeostasis via Bcl2 family proteins, CHOP and Beclin-1. In this review article we first briefly discuss arboviruses, influenza virus, and HIV and then describe the concepts of apoptosis, autophagy, and UPR. Finally, we focus upon how apoptosis, autophagy, and UPR are involved in the regulation of cellular responses to arboviruses, influenza virus and HIV infections. Abbreviation: AIDS: Acquired Immunodeficiency Syndrome; ATF6: Activating Transcription Factor 6; ATG6: Autophagy-specific Gene 6; BAG3: BCL Associated Athanogene 3; Bak: BCL-2-Anatagonist/Killer1; Bax; BCL-2: Associated X protein; Bcl-2: B cell Lymphoma 2x; BiP: Chaperon immunoglobulin heavy chain binding Protein; CARD: Caspase Recruitment Domain; cART: combination Antiretroviral Therapy; CCR5: C-C Chemokine Receptor type 5; CD4: Cluster of Differentiation 4; CHOP: C/EBP homologous protein; CXCR4: C-X-C Chemokine Receptor Type 4; Cyto c: Cytochrome C; DCs: Dendritic Cells; EDEM1: ER-degradation enhancing-a-mannosidase-like protein 1; ENV: Envelope; ER: Endoplasmic Reticulum; FasR: Fas Receptor;G2: Gap 2; G2/M: Gap2/Mitosis; GFAP: Glial Fibrillary Acidic Protein; GP120: Glycoprotein120; GP41: Glycoprotein41; HAND: HIV Associated Neurodegenerative Disease; HEK: Human Embryonic Kidney; HeLa: Human Cervical Epithelial Carcinoma; HIV: Human Immunodeficiency Virus; IPS-1: IFN-β promoter stimulator 1; IRE-1: Inositol Requiring Enzyme 1; IRGM: Immunity Related GTPase Family M protein; LAMP2A: Lysosome Associated Membrane Protein 2A; LC3: Microtubule Associated Light Chain 3; MDA5: Melanoma Differentiation Associated gene 5; MEF: Mouse Embryonic Fibroblast; MMP: Mitochondrial Membrane Permeabilization; Nef: Negative Regulatory Factor; OASIS: Old Astrocyte Specifically Induced Substrate; PAMP: Pathogen-Associated Molecular Pattern; PERK: Pancreatic Endoplasmic Reticulum Kinase; PRR: Pattern Recognition Receptor; Puma: P53 Upregulated Modulator of Apoptosis; RIG-I: Retinoic acid-Inducible Gene-I; Tat: Transactivator Protein of HIV; TLR: Toll-like receptor; ULK1: Unc51 Like Autophagy Activating Kinase 1; UPR: Unfolded Protein Response; Vpr: Viral Protein Regulatory; XBP1: X-Box Binding Protein 1.
Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Arboviruses; Autophagy; HIV; Host Microbial Interactions; Humans; Mice; Orthomyxoviridae; Signal Transduction; Stress, Physiological; Unfolded Protein Response
PubMed: 30966844
DOI: 10.1080/21505594.2019.1605803 -
Viruses Oct 2021The innate immune system is the host's first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must... (Review)
Review
The innate immune system is the host's first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology.
Topics: Animals; Epithelial Cells; Humans; Immunity, Innate; Influenza A virus; Influenza, Human; Lung; Orthomyxoviridae; Orthomyxoviridae Infections; Respiratory Tract Infections
PubMed: 34696520
DOI: 10.3390/v13102090