Virus surface glycoproteins

FIGURE 25 11 Diagram of a cell surface glycoprotein showing the disaccharide unit that IS recognized by an invading influenza virus... 

A variety of cellular and viral proteins contain fatty acids covalently bound via ester linkages to the side chains of cysteine and sometimes to serine or threonine residues within a polypeptide chain (Figure 9.18). This type of fatty acyl chain linkage has a broader fatty acid specificity than A myristoylation. Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the Cjg and Cjg chain lengths being most commonly found. Proteins anchored to membranes via fatty acyl thioesters include G-protein-coupled receptors, the surface glycoproteins of several viruses, and the transferrin receptor protein. 

Neuraminidase inhibitors are the major class of drugs to treat or to prevent the infection with influenza viruses. Currently, two neuraminidase inhibitors are available, zanamivir and oseltamivir, which block the release of new influenza vims from infected host cells and thereby stop the spread of infection. The enzyme neuraminidase is a surface glycoprotein present on all influenza viruses. There are nine influenza neuraminidase sub-types known of which subtypes N1 and N2 appear to be the most important ones. Neuraminidase inhibitors are effective against all neuraminidase subtypes. The activity of the neuraminidase is required for the newly... 

Alirezaei M, Watry DD, Flynn CF, Kiosses WB, Mashah E, Williams BR, Kaul M, Lipton SA, Fox HS (2007) Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons. J Neurosci 27(41) 11047-11055... 

One experimental tool in this direction is provided by some enveloped animal viruses which mature at the cell surface of infected cells (K Sri inen and Renkonen, 1977 Lenard, 1978). Such viruses include influenza virus, Semliki Forest virus (SFV), Sindbis virus, and vesicular stomatitis virus (VSV). They are extremely simple in makeup and hence are very well characterized. They can be tagged with biochemical probes in many different ways. They infect many animal cells in culture, and after infection turn the cells into factories for the production of virus progeny. The protein-synthesizing machinery of the host cell is programmed by the viral RNA to make viral proteins exclusively and these include the viral surface glycoproteins. These are synthesized with signal peptides and inserted into the ER membrane (Katz et ai, 1977 Garoff et... 

Influenza A infections are responsible for 300-500,000 deaths and 3-5 million hospitalizations per year. Every epidemic brings about new strains of influenza A, which arise due to point mutations within the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). These mutations in turn enable emerging virus strains to evade the host s immune system. The long production time of the current commercially available vaccine, which is produced in chicken eggs, is a major obstacle. 

Ashraf, S., Singh, P.K., Yadav, D.K., Shahnawuz, M., Mishra, S., Sawant, S.V., and Tuli, R. (2005). High level expression of surface glycoprotein of rabies virus in tobacco and its immunoprotective activity in mice. J. Biotechnol. 119(1) 1-14. 

Virosomes are viral glycoproteins encapsulated in lipid vesicles, which have been shown to be effective as experimental vaccines delivered by both mucosal and systemic routes. Viruses and their surface glycoproteins have a high affinity for receptors on mucosal surfaces, especially along the respiratory tract. 

However, infrequently a mutation arises by genetic reassortment of viruses from different animal hosts ( Antigenic Shift ) whereby an entirely new gene for one of the surface glycoproteins is generated that is significantly different (-50%) in amino acid sequence from the parent virus. This is the mechanism by which new subtypes of influenza arise and are primarily responsible for the major pandemics that occur. 

If all the sugar residues of the glycophorin molecules in an erythrocyte were spread over the surface of the cell they could cover approximately one-fifth of its surface in a loose network. However, it is more likely that they form bushy projections of a more localized sort. These oligosaccharides not only act as immunological determinants but also serve as receptors for influenza viruses. Other glycoproteins related to glycophorin A occur in smaller amounts.244... 

The initial event in the entry of viruses into cells is the attachment of the virus to specific receptors on the cell membrane. The chemical structures of most receptors for animal viruses are poorly defined. Cell surface glycoprotein, glycolipids, and phospholipids have been implicated. Very recently Helenius et al. (29) could identify human HLA and murine H-2 histocompatibility antigens as receptors for Semliki Forest virus these antigens are well-defined membrane glycoproteins. 

Sendai virus, like other myxo- and paramyxovirus, has surface glycoprotein spikes which adsorb to specific receptors on erythrocytes of most mammalian and fowl species and cause hemagglutination. The receptors on erythrocyte membranes contain neuraminic acid, as indicated by the fact that they are destroyed by neuraminidase. Haywood (3 ) demonstrated that liposomes containing gangliosides could inhibit the agglutination of erythro-... 

The essential roles, although controversial at times, played by both of these surface glycoproteins in the infectious life cycle of the virus, coupled with a... 

Examples of glyco-coated dendrimers are the sialylated dendrimers79 that have been developed to prevent infection by the influenza virus. This infection is mediated by the interaction of viral glycoprotein hemagglutinin and the sialic acid residues present on cell-surface glycoproteins and glycolipids. 

Figure 1 Electron micrograph of an artificial viral envelope. In a unilamellar lipid bilayer of a diameter of approximately 200 nm are surface glycoproteins of the respiratory syncytial virus (RSV) inserted as described in detail by Chander Schreier [7] (electron micrographic image by G. Erdos, EM Core Laboratory, University of Florida, Gainesville, EL).

The addition of sugars is often required for a glycoprotein to function properly and reach its ultimate destination in the cell or organism. Glycoproteins are ffequendy present at the surface of cells where they function as membrane proteins or as part of the extracellular matrix. These cell surface glycoproteins play a critical role in cell-cell interactions and the mechanisms of infection by bacteria and viruses. 

Chimeric molecules composed of regions of the HIV virus receptor and immunoglobulins, dubbed immunoadhesins , are under development as therapeutics for AIDS. HIV enters its preferred host cell, the helper T lymphocyte, by interaction between the viral surface glycoprotein, gpl20 and a transmembrane... 

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