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Clinical Microbiology Reviews Jan 1992Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic... (Review)
Review
Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands.
Topics: Animals; Base Sequence; Humans; Influenza Vaccines; Molecular Sequence Data; Orthomyxoviridae; Orthomyxoviridae Infections; Viral Proteins
PubMed: 1310439
DOI: 10.1128/CMR.5.1.74 -
Viruses Apr 2021Hemagglutinin and neuraminidase, which constitute the glycoprotein spikes expressed on the surface of influenza A and B viruses, are the most exposed parts of the virus... (Review)
Review
Hemagglutinin and neuraminidase, which constitute the glycoprotein spikes expressed on the surface of influenza A and B viruses, are the most exposed parts of the virus and play critical roles in the viral lifecycle. As such, they make prominent targets for the immune response and antiviral drugs. Neuraminidase inhibitors, particularly oseltamivir, constitute the most commonly used antivirals against influenza viruses, and they have proved their clinical utility against seasonal and emerging influenza viruses. However, the emergence of resistant strains remains a constant threat and consideration. Antivirals targeting the hemagglutinin protein are relatively new and have yet to gain global use but are proving to be effective additions to the antiviral repertoire, with a relatively high threshold for the emergence of resistance. Here we review antiviral drugs, both approved for clinical use and under investigation, that target the influenza virus hemagglutinin and neuraminidase proteins, focusing on their mechanisms of action and the emergence of resistance to them.
Topics: Animals; Antiviral Agents; Clinical Trials as Topic; Drug Resistance, Viral; Enzyme Inhibitors; Hemagglutinins, Viral; Humans; Influenza, Human; Mice; Neuraminidase; Orthomyxoviridae; Orthomyxoviridae Infections; Oseltamivir; Viral Envelope Proteins
PubMed: 33917376
DOI: 10.3390/v13040624 -
Biophysical Journal Jun 2014During replication, the physical state of a virus is controlled by assembly and disassembly processes, when particles are put together and dismantled by cellular cues,... (Review)
Review
During replication, the physical state of a virus is controlled by assembly and disassembly processes, when particles are put together and dismantled by cellular cues, respectively. A fundamental question has been how a cell can assemble an infectious virus, and dismantle a virus entering an uninfected cell and thereby trigger a new round of infection. This apparent paradox might be explained by considering that infected and uninfected cells are functionally different, or that assembly and disassembly take place along different cellular pathways. A third possibility is that the physical properties of newly assembled viruses are different from the infection-ready viruses. Recent biophysical experiments measured the stiffness of single Influenza viruses and combined this with biochemical measurements and cell biological assays. Besides inducing the fusogenic state of hemagglutinin, low pH cues softened the virus and precluded aggregation of viral ribonucleoprotein particles with the matrix protein M1. The recent experiments suggest a two-step model for Influenza virus entry and uncoating involving low pH in early and late endosomes, respectively. I conclude with a short outlook into how combined biophysical and cell biological approaches might lead to the identification of new cellular cues controlling viral uncoating and infection.
Topics: Animals; Endosomes; Host-Pathogen Interactions; Humans; Hydrogen-Ion Concentration; Orthomyxoviridae; Orthomyxoviridae Infections; Viral Structural Proteins
PubMed: 24896110
DOI: 10.1016/j.bpj.2014.04.025 -
Veterinaria Italiana Sep 2019Each year millions of people are infected by influenza viruses, and this causes a substantial economic and health burden on our society. Influenza epidemics and... (Review)
Review
Each year millions of people are infected by influenza viruses, and this causes a substantial economic and health burden on our society. Influenza epidemics and pandemics are attributable to the ongoing evolution of influenza viruses through antigenic drift and shift, respectively. One of the reasons for the continuous circulation of influenza viruses in the human population is the incomplete protection conferred by currently available seasonal influenza vaccines against possible arising drifted or shifted influenza strains. Recently, tremendous efforts have been focused on the development of a more effective broadly reactive or universal influenza vaccine. The main objective of underdevelopment vaccines is to protect the human population not only from currently circulating virus strains but also from possible future variants without the need for their continuous update. Different approaches have been developed to reach this goal and elicit an effective and cross-protective immune response. Among these, consensus-based prophylactic approaches to effectively prevent influenza infections are the major focus of this review.
Topics: Animals; Hemagglutinins; Humans; Influenza, Human; Orthomyxoviridae; Orthomyxoviridae Infections
PubMed: 31599544
DOI: 10.12834/VetIt.1944.10352.1 -
Emerging Infectious Diseases Apr 2015Wild birds play a major role in the evolution, maintenance, and spread of avian influenza viruses. However, surveillance for these viruses in wild birds is sporadic,... (Review)
Review
Wild birds play a major role in the evolution, maintenance, and spread of avian influenza viruses. However, surveillance for these viruses in wild birds is sporadic, geographically biased, and often limited to the last outbreak virus. To identify opportunities to optimize wild bird surveillance for understanding viral diversity, we reviewed responses to a World Organisation for Animal Health-administered survey, government reports to this organization, articles on Web of Knowledge, and the Influenza Research Database. At least 119 countries conducted avian influenza virus surveillance in wild birds during 2008-2013, but coordination and standardization was lacking among surveillance efforts, and most focused on limited subsets of influenza viruses. Given high financial and public health burdens of recent avian influenza outbreaks, we call for sustained, cost-effective investments in locations with high avian influenza diversity in wild birds and efforts to promote standardized sampling, testing, and reporting methods, including full-genome sequencing and sharing of isolates with the scientific community.
Topics: Animals; Animals, Wild; Birds; Cost-Benefit Analysis; Databases, Factual; Genetic Variation; Global Health; Humans; Influenza in Birds; Mandatory Reporting; Orthomyxoviridae; Population Surveillance; Web Browser
PubMed: 25811221
DOI: 10.3201/eid2104.141415 -
European Journal of Pharmacology Aug 2017The influenza virus (IV) is a highly contagious virus causing seasonal global outbreaks affecting annually up to 20% of the world's population and leading to... (Review)
Review
The influenza virus (IV) is a highly contagious virus causing seasonal global outbreaks affecting annually up to 20% of the world's population and leading to 250,000-500,000 deaths worldwide. Current vaccines have variable effectiveness, and, in particular during a pandemic outbreak, they are probably not available in the amounts needed to protect the world population. Therefore we need effective small molecule drugs to combat an IV infection and that can be produced, in case of pandemic, rapidly and in large quantities. Unfortunately, natural occurring IV becomes more and more resistant to current anti-IV drugs. And thus, there is an urgent need for development of alternative agents with new mechanisms of action. This review provides an overview of the pharmacology and effectiveness of new anti-IV agents, focusing on inhibition mechanisms directed against virus-host interactions.
Topics: Animals; Antiviral Agents; Drug Interactions; Host-Pathogen Interactions; Humans; Influenza, Human; Orthomyxoviridae
PubMed: 28533172
DOI: 10.1016/j.ejphar.2017.05.038 -
Virus Research Dec 2004Influenza viruses are causative agents of an acute febrile respiratory disease called influenza (commonly known as "flu") and belong to the Orthomyxoviridae family.... (Review)
Review
Influenza viruses are causative agents of an acute febrile respiratory disease called influenza (commonly known as "flu") and belong to the Orthomyxoviridae family. These viruses possess segmented, negative stranded RNA genomes (vRNA) and are enveloped, usually spherical and bud from the plasma membrane (more specifically, the apical plasma membrane of polarized epithelial cells). Complete virus particles, therefore, are not found inside infected cells. Virus particles consist of three major subviral components, namely the viral envelope, matrix protein (M1), and core (viral ribonucleocapsid [vRNP]). The viral envelope surrounding the vRNP consists of a lipid bilayer containing spikes composed of viral glycoproteins (HA, NA, and M2) on the outer side and M1 on the inner side. Viral lipids, derived from the host plasma membrane, are selectively enriched in cholesterol and glycosphingolipids. M1 forms the bridge between the viral envelope and the core. The viral core consists of helical vRNP containing vRNA (minus strand) and NP along with minor amounts of NEP and polymerase complex (PA, PB1, and PB2). For viral morphogenesis to occur, all three viral components, namely the viral envelope (containing lipids and transmembrane proteins), M1, and the vRNP must be brought to the assembly site, i.e. the apical plasma membrane in polarized epithelial cells. Finally, buds must be formed at the assembly site and virus particles released with the closure of buds. Transmembrane viral proteins are transported to the assembly site on the plasma membrane via the exocytic pathway. Both HA and NA possess apical sorting signals and use lipid rafts for cell surface transport and apical sorting. These lipid rafts are enriched in cholesterol, glycosphingolipids and are relatively resistant to neutral detergent extraction at low temperature. M1 is synthesized on free cytosolic polyribosomes. vRNPs are made inside the host nucleus and are exported into the cytoplasm through the nuclear pore with the help of M1 and NEP. How M1 and vRNPs are directed to the assembly site on the plasma membrane remains unclear. The likely possibilities are that they use a piggy-back mechanism on viral glycoproteins or cytoskeletal elements. Alternatively, they may possess apical determinants or diffuse to the assembly site, or a combination of these pathways. Interactions of M1 with M1, M1 with vRNP, and M1 with HA and NA facilitate concentration of viral components and exclusion of host proteins from the budding site. M1 interacts with the cytoplasmic tail (CT) and transmembrane domain (TMD) of glycoproteins, and thereby functions as a bridge between the viral envelope and vRNP. Lipid rafts function as microdomains for concentrating viral glycoproteins and may serve as a platform for virus budding. Virus bud formation requires membrane bending at the budding site. A combination of factors including concentration of and interaction among viral components, increased viscosity and asymmetry of the lipid bilayer of the lipid raft as well as pulling and pushing forces of viral and host components are likely to cause outward curvature of the plasma membrane at the assembly site leading to bud formation. Eventually, virus release requires completion of the bud due to fusion of the apposing membranes, leading to the closure of the bud, separation of the virus particle from the host plasma membrane and release of the virus particle into the extracellular environment. Among the viral components, M1 contains an L domain motif and plays a critical role in budding. Bud completion requires not only viral components but also host components. However, how host components facilitate bud completion remains unclear. In addition to bud completion, influenza virus requires NA to release virus particles from sialic acid residues on the cell surface and spread from cell to cell. Elucidation of both viral and host factors involved in viral morphogenesis and budding may lead to the development of drugs interfering with the steps of viral morphogenesis and in disease progression.
Topics: Animals; Humans; Nucleocapsid; Orthomyxoviridae; Protein Transport; Viral Matrix Proteins; Viral Proteins; Virus Assembly
PubMed: 15567494
DOI: 10.1016/j.virusres.2004.08.012 -
Viruses Nov 2020Tilapia lake virus (TiLV) has caused mass mortalities in farmed and wild tilapia with serious economic and ecological consequences. Until recently, this virus was the...
Tilapia lake virus (TiLV) has caused mass mortalities in farmed and wild tilapia with serious economic and ecological consequences. Until recently, this virus was the sole member of the , a family within the order comprising segmented negative-sense RNA viruses. We sought to identify additional viruses within the through total RNA sequencing (meta-transcriptomics) and data mining of published transcriptomes. Accordingly, we sampled marine fish species from both Australia and China and discovered several segments of two new viruses within the , tentatively called and , respectively. In addition, by mining vertebrate transcriptome data, we identified nine additional virus transcripts matching to multiple genomic segments of TiLV in both marine and freshwater fish. These new viruses retained sequence conservation with the distantly related in the RdRp subunit PB1, but formed a distinct and diverse phylogenetic group. These data suggest that the have a broad host range within fish and that greater animal sampling will identify additional divergent members of the .
Topics: Animals; Australia; China; Computational Biology; Data Mining; Fish Diseases; Host Specificity; Orthomyxoviridae; Orthomyxoviridae Infections; Phylogeny; Sequence Analysis, RNA; Tilapia; Transcriptome
PubMed: 33158212
DOI: 10.3390/v12111254 -
Influenza and Other Respiratory Viruses Nov 2010Equine influenza virus (EIV) is considered the most important respiratory virus of horses because it is highly contagious and has the potential to disrupt major... (Review)
Review
Equine influenza virus (EIV) is considered the most important respiratory virus of horses because it is highly contagious and has the potential to disrupt major equestrian events. Equine influenza (EI) can be controlled by vaccination but it has been demonstrated repeatedly in the field that antigenic drift impacts on vaccine efficacy. EI surveillance maintains awareness of emergence and international spread of antigenic variants. It not only serves as an early warning system for horse owners, trainers and veterinary clinicians but is fundamental to influenza control programmes based on vaccination. Data on outbreaks of EI and strain characterisation is reviewed annually by an Expert Surveillance Panel (ESP) including representatives from OIE and WHO. This panel makes recommendations on the need to update vaccines based on analysis of evidence of disease in well vaccinated horses, antigenic changes, genetic changes and when possible, experimental challenge data. However, the disparity in the level of surveillance and virus collection in different countries results in potentially biased information about the relative prevalence of different viruses. There is a need for increased surveillance on a global level and a greater awareness of the benefits of updating the vaccines. The vaccine companies have traditionally been slow to respond to the ESP recommendations. Veterinary clinicians have a major role to play in purchasing vaccines with epidemiologically relevant strains and promoting their benefits to their clients.
Topics: Animals; Disease Outbreaks; Horse Diseases; Horses; Influenza Vaccines; Orthomyxoviridae; Orthomyxoviridae Infections; Sentinel Surveillance
PubMed: 20958927
DOI: 10.1111/j.1750-2659.2010.00176.x -
Virus Research Nov 2015The host interferon (IFN) response represents one of the first barriers that influenza viruses must surmount in order to establish an infection. Many advances have been... (Review)
Review
The host interferon (IFN) response represents one of the first barriers that influenza viruses must surmount in order to establish an infection. Many advances have been made in recent years in understanding the interactions between influenza viruses and the interferon system. In this review, we summarise recent work regarding activation of the type I IFN response by influenza viruses, including attempts to identify the viral RNA responsible for IFN induction, the stage of the virus life cycle at which it is generated and the role of defective viruses in this process.
Topics: Defective Viruses; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferon Type I; Orthomyxoviridae
PubMed: 25678267
DOI: 10.1016/j.virusres.2015.02.003