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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 -
Cold Spring Harbor Perspectives in... Oct 2021Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid-containing, cell-surface glycoconjugates... (Review)
Review
Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid-containing, cell-surface glycoconjugates as receptors but have limited affinity for them, and, as a consequence, virus attachment to cells requires their interaction with several virus HAs. Receptor-bound virus is transferred into endosomes where membrane fusion by HAs is activated at pH between 5 and 6.5, depending on the strain of virus. Fusion activity requires extensive rearrangements in HA conformation that include extrusion of a buried "fusion peptide" to connect with the endosomal membrane, form a bridge to the virus membrane, and eventually bring both membranes close together. In this review, we give an overview of the structures of the 16 genetically and antigenically distinct subtypes of influenza A HA in relation to these two functions in virus replication and in relation to recognition of HA by antibodies that neutralize infection.
Topics: Hemagglutinins; Humans; Hydrogen-Ion Concentration; Membrane Fusion; Orthomyxoviridae
PubMed: 32513673
DOI: 10.1101/cshperspect.a038638 -
Trends in Microbiology Mar 2023Influenza virus contains a single-stranded negative-sense RNA genome. Replication of the genome is carried out by the viral RNA-dependent RNA polymerase in the context... (Review)
Review
Influenza virus contains a single-stranded negative-sense RNA genome. Replication of the genome is carried out by the viral RNA-dependent RNA polymerase in the context of the viral ribonucleoprotein (RNP) complex, through a positive-sense complementary RNA intermediate. Genome replication is tightly controlled through interactions with accessory viral and host factors. Propelled by developments in recombinant protein expression, and technical improvements in X-ray crystallography and cryo-electron microscopy, snapshots of the replication process have been captured. Here, we review how recent structural data shed light on the molecular mechanisms of influenza virus genome replication, in particular, encapsidation of nascent RNA, de novo RNP assembly, and regulation of replication initiation through interactions with host and viral cues.
Topics: Humans; Ribonucleoproteins; Cryoelectron Microscopy; RNA, Viral; Virus Replication; Orthomyxoviridae; Influenza, Human
PubMed: 36336541
DOI: 10.1016/j.tim.2022.09.015 -
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 -
Viruses Jul 2022Influenza viruses are responsible for millions of cases globally and significantly threaten public health. Since pandemic and zoonotic influenza viruses have emerged in... (Review)
Review
Influenza viruses are responsible for millions of cases globally and significantly threaten public health. Since pandemic and zoonotic influenza viruses have emerged in the last 20 years and some of the viruses have resulted in high mortality in humans, a universal influenza vaccine is needed to provide comprehensive protection against a wide range of influenza viruses. Current seasonal influenza vaccines provide strain-specific protection and are less effective against mismatched strains. The rapid antigenic drift and shift in influenza viruses resulted in time-consuming surveillance and uncertainty in the vaccine protection efficacy. Most recent universal influenza vaccine studies target the conserved antigen domains of the viral surface glycoproteins and internal proteins to provide broader protection. Following the development of advanced vaccine technologies, several innovative strategies and vaccine platforms are being explored to generate robust cross-protective immunity. This review provides the latest progress in the development of universal influenza vaccines.
Topics: Antibodies, Viral; Humans; Influenza Vaccines; Influenza, Human; Orthomyxoviridae; Orthomyxoviridae Infections
PubMed: 36016306
DOI: 10.3390/v14081684 -
Virus Research Oct 2020Since swine influenza virus was first isolated in 1930, it has become endemic in pigs worldwide. Although large amount of swine influenza vaccines has been used in swine... (Review)
Review
Since swine influenza virus was first isolated in 1930, it has become endemic in pigs worldwide. Although large amount of swine influenza vaccines has been used in swine industry, swine influenza still cannot be efficiently controlled and has been an important economic disease for swine industry. The high diversity and varied distribution of different subtypes and genotypes of swine influenza viruses circulating in pigs globally is a major challenge to produce broadly effective vaccines and control disease. Importantly, swine influenza virus is able to cross species barrier to infect humans and even caused influenza pandemic in 2009. Herein, current status and challenge of swine influenza viruses is reviewed and discussed.
Topics: Animals; Genotype; Humans; Influenza A virus; Influenza Vaccines; Influenza, Human; Orthomyxoviridae Infections; Public Health; Reassortant Viruses; Swine; Swine Diseases
PubMed: 32798539
DOI: 10.1016/j.virusres.2020.198118 -
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 -
Signal Transduction and Targeted Therapy Apr 2023Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and... (Review)
Review
Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches. Currently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parainfluenza virus, measles virus, Newcastle disease virus, influenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors that differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective efficacy. This review summarized the overall profile of the design strategies, progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.
Topics: Animals; Humans; Viral Vaccines; Genetic Vectors; Orthomyxoviridae; Communicable Diseases; Adenoviridae
PubMed: 37029123
DOI: 10.1038/s41392-023-01408-5 -
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 -
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