Influenza virus enveloped particles

RNA viruses Myxovi ruses Influenza virus Enveloped particles, 100nm in diameterwith a helically symmetric These viruses are capable of extensive antigenic variation, producing new types against which the human population does not have effective immunity. These new antigenic... 

Immunopotentiating reconstituted influenza virosomes (IRTV) are spherical 150-nm sized particles consisting of a phospholipid bilayer in which influenza virus A/Singapore strain-derived hemagglutinin (HA) and neuraminidase (NA) are intercalated. As such, they resemble and mimic the influenza virus envelope. The difference from conventional liposome formulations lies in the inclusion of the viral envelope proteins HA and NA as well as viral phospholipids. Especially, the inclusion of influenza virus HA provides IRIV with delivery and immimogenic capacities. IRTV are licensed for human use as adjuvant in hepatitis A vaccination and as influenza subunit vaccine (1). 

The influenza virus inhibitors, zanamivir, and oseltamivir, act outside the cell after virus particles have been formed. The dtugs have been designed to fit into the active site of the viral envelope enzyme neuraminidase, which is required to cleave sialic acid off the surface of the producing cells. When its activity is blocked, new virus particles stay attached to the cell surface through binding of the virus protein hemagglutinin to sialic acid and are prevented from spreading to other cells. 

Helical symmetry was thought at one time to exist only in plant viruses. It is now known, however, to occur in a number of animal virus particles. The influenza and mumps viruses, for example, which were first seen in early electron micrographs as roughly spherical particles, have now been observed as enveloped particles within the envelope, the capsids themselves are helically symmetrical and appear similar to the rods of TMV, except that they are more flexible and are wound like coils of rope in the centre of the particle. 

Influenza virus particles are spheroidal and approximately 100 nm in diameter. The outer-membrane envelope contains 500 copies of hemagglutinin (HA) trimers and 100 copies of neuraminidase tetramers. The hemagglutinin constitutes the receptor sites for a-sialoside ligands. X-ray analyses show that the three sialic acid binding pockets reside 46 A apart, each trimer being separated on the virion surface by about 65-110 A [42],... 

For enveloped viruses such as the influenza viruses it has been shown that similar binding affinities are found for the hemagglutinin (HA) Hg-and sialic acid using either isolated HA or the whole virus [37,40] using simple H NMR titration experiments. In contrast to structural proteins of non-enveloped viruses, HA is a membrane protein and thus not as rigid as proteins as part of, e.g., icosahedral particles. For the application of STD NMR... 

Budding and release of progeny virus. B. Replicative cycle of an influenza virus, an example of an RNA virus. 1. Attachment. 2. Endocytosis. 3. Influx of H+ through M2 protein. 4. Fusion of the viral envelope with the endosomes membrane, dissociation of the RNP complex, and entry of viral RNA into the nucleus. 5. Synthesis of viral mRNA by viral RNA polymerase. 6. Translation of viral mRNA by host cell s ribosomes. 7. Replication of viral RNA, using viral RNA polymerase, via cRNA replicative form. 8. Assembly of virus particles, and 9. Budding and release of progeny virus. 

All enveloped human viruses acquire their phospholipid coating by budding through cellular membranes. For example, with the influenza virus, the capsid protein subunits are transported from the ribosomes to the nucleus, where they combine with new viral RNA molecules and are assembled into the helical capsids. The haemagglutinin and neuraminidase proteins that project from the envelope of the normal particles migrate to the cytoplasmic membrane where they displace the normal cell membrane proteins. The assembled nucleocapsids finally pass out from the nucleus, and as they impinge on the altered cytoplasmic membrane they cause it to bulge and bud off completed enveloped particles from the cell. 

Influenza virus neuraminidase Influenza Viral envelope glycoprotein involved in viral release, cleavage of sialic add residues of new virus particles and host membranes Inhibition at active site... 

Fig.1. Viruses. Schematic representation of virus particles, all drawn to scale. The type of genome (RNA or DNA) is shown in brackets. Enveloped viruses 1 Pox virus (DNA). 2 Rabies virus (RNA). 3 Influenza virus (RNA). 4 Measles virus (RNA). 5 Chickenpox virus (ONA). Naked or unenveloped viruses 6 Yellow fever virus (RNA). 7 Adenovirus (DNA). 8 Reovirus (RNA). 9 Wart-papilloma virus (ONA). 10 Poliomyelitis virus (RNA). 11 Parvovirus (RNA). 12 Corona virus (RNA). 13 Tobacco mosaic virus (RNA). 14 Bacteriophage T2 (DNA).

Interesting observations have also been made by Shao and Zhang [31], who used cryo-AFM to investigate the effect of osmotic stress on the influenza virus, where the virus was first adsorbed onto mica, where excess particles were removed. The remaining surface particles were then immersed in deionised water, producing osmotic shock, which caused the capsid envelope to burst and release RNA. Here the rupture pore was also clearly visible, allowing the internal structure to be analysed. 

During endocytosis, the association between receptor and anti-receptor draws the cell membrane to engulf the virus particle forming a cytosolic vacuole, similar to the process by which cells ingest other materials. Probably all non-enveloped viruses penetrate the cell in this manner, but some enveloped viruses such as orthomyxoviruses (e.g. influenza) also use this process. 

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