-
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 -
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 -
Cell Host & Microbe Jun 2010Newly emerging or "re-emerging" viral diseases continue to pose significant global public health threats. Prototypic are influenza viruses that are major causes of human... (Review)
Review
Newly emerging or "re-emerging" viral diseases continue to pose significant global public health threats. Prototypic are influenza viruses that are major causes of human respiratory infections and mortality. Influenza viruses can cause zoonotic infections and adapt to humans, leading to sustained transmission and emergence of novel viruses. Mechanisms by which viruses evolve in one host, cause zoonotic infection, and adapt to a new host species remain unelucidated. Here, we review the evolution of influenza A viruses in their reservoir hosts and discuss genetic changes associated with introduction of novel viruses into humans, leading to pandemics and the establishment of seasonal viruses.
Topics: Adaptation, Biological; Animals; Disease Outbreaks; Evolution, Molecular; Humans; Influenza, Human; Orthomyxoviridae; Zoonoses
PubMed: 20542248
DOI: 10.1016/j.chom.2010.05.009 -
Advances in Experimental Medicine and... 2012As all the enveloped viruses, the entry of influenza viruses includes a number of steps in host cell infection. This chapter summarizes the current knowledge of the... (Review)
Review
As all the enveloped viruses, the entry of influenza viruses includes a number of steps in host cell infection. This chapter summarizes the current knowledge of the entry pathway and the role of the fusion protein of influenza virus, hemagglutinin, in this process. Hemagglutinin (HA) is a trimeric glycoprotein that is present in multiple copies in the membrane envelope of influenza virus. HA contains a fusion peptide, a receptor binding site, a metastable structural motif, and the transmembrane domain. The first step of influenza virus entry is the recognition of the host cell receptor molecule, terminal α-sialic acid, by HA. This multivalent attachment by multiple copies of trimetric HA triggers endocytosis of influenza virus that is contained in the endosome. The endosome-trapped virus traffics via a unidirectional pathway to near the nucleus. At this location, the interior pH of the endosome becomes acidic that induces a dramatic conformational change in HA to insert the fusion peptide into the host membrane, induce juxtaposition of the two membranes, and form a fusion pore that allows the release of the genome segments of influenza virus. HA plays a key role in the entire entry pathway. Inhibitors of virus entry are potentially effective antiviral drugs of influenza viruses.
Topics: Antiviral Agents; Binding Sites; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Hydrogen-Ion Concentration; Models, Molecular; Orthomyxoviridae; Protein Structure, Tertiary; Virus Internalization
PubMed: 22297515
DOI: 10.1007/978-1-4614-0980-9_9 -
Vaccine Sep 2008The influenza viruses are characterized by segmented, negative-strand RNA genomes requiring an RNA-dependent RNA polymerase of viral origin for replication. The... (Review)
Review
The influenza viruses are characterized by segmented, negative-strand RNA genomes requiring an RNA-dependent RNA polymerase of viral origin for replication. The particular structure ofthe influenza virus genome and function of its viral proteins enable antigenic drift and antigenic shift. These processes result in viruses able to evade the long-term adaptive immune responses in many hosts.
Topics: Antigens, Viral; Genetic Drift; Orthomyxoviridae; Reassortant Viruses
PubMed: 19230160
DOI: 10.1016/j.vaccine.2008.07.039 -
Viruses Apr 2016Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America,... (Review)
Review
Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000-50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans.
Topics: Animals; Cell Culture Techniques; Fluorescent Antibody Technique, Direct; Humans; Immunoassay; Influenza, Human; Lab-On-A-Chip Devices; Molecular Diagnostic Techniques; Orthomyxoviridae; Sequence Analysis, DNA; Serologic Tests
PubMed: 27077877
DOI: 10.3390/v8040096 -
Medicina (Kaunas, Lithuania) 2007Every year, especially during the cold season, many people catch an acute respiratory disease, namely flu. It is easy to catch this disease; therefore, it spreads very... (Comparative Study)
Comparative Study Review
Every year, especially during the cold season, many people catch an acute respiratory disease, namely flu. It is easy to catch this disease; therefore, it spreads very rapidly and often becomes an epidemic or a global pandemic. Airway inflammation and other body ailments, which form in a very short period, torment the patient several weeks. After that, the symptoms of the disease usually disappear as quickly as they emerged. The great epidemics of flu have rather unique characteristics; therefore, it is possible to identify descriptions of such epidemics in historic sources. Already in the 4th century bc, Hippocrates himself wrote about one of them. It is known now that flu epidemics emerge rather frequently, but there are no regular intervals between those events. The epidemics can differ in their consequences, but usually they cause an increased mortality of elderly people. The great flu epidemics of the last century took millions of human lives. In 1918-19, during "The Spanish" pandemic of flu, there were around 40-50 millions of deaths all over the world; "Pandemic of Asia" in 1957 took up to one million lives, etc. Influenza virus can cause various disorders of the respiratory system: from mild inflammations of upper airways to acute pneumonia that finally results in the patient's death. Scientist Richard E. Shope, who investigated swine flu in 1920, had a suspicion that the cause of this disease might be a virus. Already in 1933, scientists from the National Institute for Medical Research in London - Wilson Smith, Sir Christopher Andrewes, and Sir Patrick Laidlaw - for the first time isolated the virus, which caused human flu. Then scientific community started the exhaustive research of influenza virus, and the great interest in this virus and its unique features is still active even today.
Topics: Adolescent; Adult; Age Factors; Aged; Animals; Antigenic Variation; Antigens, Viral; Birds; Child; Child, Preschool; Disease Outbreaks; Ecology; Genome, Viral; History, 20th Century; Humans; Influenza A virus; Influenza B virus; Influenza in Birds; Influenza, Human; Gammainfluenzavirus; Mammals; Middle Aged; Orthomyxoviridae; Orthomyxoviridae Infections; Swine; Virus Replication
PubMed: 18182834
DOI: No ID Found -
Viruses Aug 2016The advent of virus reverse genetics has enabled the incorporation of genetically encoded reporter proteins into replication-competent viruses. These reporters include... (Review)
Review
The advent of virus reverse genetics has enabled the incorporation of genetically encoded reporter proteins into replication-competent viruses. These reporters include fluorescent proteins which have intrinsic chromophores that absorb light and re-emit it at lower wavelengths, and bioluminescent proteins which are luciferase enzymes that react with substrates to produce visible light. The incorporation of these reporters into replication-competent viruses has revolutionized our understanding of molecular virology and aspects of viral tropism and transmission. Reporter viruses have also enabled the development of high-throughput assays to screen antiviral compounds and antibodies and to perform neutralization assays. However, there remain technical challenges with the design of replication-competent reporter viruses, and each reporter has unique advantages and disadvantages for specific applications. This review describes currently available reporters, design strategies for incorporating reporters into replication-competent paramyxoviruses and orthomyxoviruses, and the variety of applications for which these tools can be utilized both in vitro and in vivo.
Topics: Animals; Genes, Reporter; Humans; Luciferases; Luminescent Measurements; Orthomyxoviridae; Reverse Genetics; Staining and Labeling
PubMed: 27527209
DOI: 10.3390/v8080214 -
The Journal of General Virology Aug 2016Clinical isolates of influenza virus produce pleomorphic virus particles, including extremely long filamentous virions. In contrast, strains of influenza that have... (Review)
Review
Clinical isolates of influenza virus produce pleomorphic virus particles, including extremely long filamentous virions. In contrast, strains of influenza that have adapted to laboratory growth typically produce only spherical virions. As a result, the filamentous phenotype has been overlooked in most influenza virus research. Recent advances in imaging and improved animal models have highlighted the distinct structure and functional relevance of filamentous virions. In this review we summarize what is currently known about these strikingly elongated virus particles and discuss their possible roles in clinical infections.
Topics: Animals; Humans; Orthomyxoviridae; Virus Assembly
PubMed: 27365089
DOI: 10.1099/jgv.0.000535 -
Viruses Mar 2021Bats are natural reservoirs for many viruses, including several that are zoonotic. Two unusual H17N10 and H18N11 influenza viruses have been found in New World bats.... (Review)
Review
Bats are natural reservoirs for many viruses, including several that are zoonotic. Two unusual H17N10 and H18N11 influenza viruses have been found in New World bats. Although neither of these viruses have been isolated, infectious clone technology has permitted significant progress to understand their biology, which include unique features compared to all other known influenza A viruses. In addition, an H9N2-like influenza A virus was isolated from Old World bats and it shows similar characteristics of normal influenza A viruses. In this review, current status and perspective on influenza A viruses identified in bats is reviewed and discussed.
Topics: Animals; Chiroptera; Humans; Influenza A Virus, H9N2 Subtype; Influenza, Human; Mice; Orthomyxoviridae; Orthomyxoviridae Infections; Viral Zoonoses; Virus Replication
PubMed: 33805956
DOI: 10.3390/v13040547