Viruses membrane glycoprotein receptor

Specific proteins on the surface of virus particles, e.g. the haemagglutinins of influenza viruses (Fig. 3.8), mediate their adherence to glycoprotein receptors in the plasma membrane of host cells. Viruses make use of a variety of membrane glycoproteins as... 

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. 

Animal V. The first stage of infection is adsorption of the vims to the exterior surface of the animal cell membrane. Adsorption occurs by interaction between a virus-coded protein on the surface of the virion and a receptor moleeule on the cell membrane. Most cell receptors are glycoproteins. Moreover, they are normal membrane glycoproteins with specific functions unrelated to virus infection. The interaction is specific. Thus, the binding protein of influenza virus interacts with the o2 3 linked terminal sialic add residue of the host cell membrane glycopFOtein treatment of a cell with sialidase (neuraminidase) renders it resistant to infection, and glycoproteins with al 6 linked siaUc acid do not serve as receptors. Under natural conditions, the presence of appropriate receptor molecules on the cell membrane is a precondition for virus infection, i.e. in the absence of receptors, the cell is not permissive for virus infection... 

A comparative immunochemical study of human erythrocyte membrane glycoprotein which uses two different extraction procedures has been reported. Each preparation contained receptors for influenza virus and was composed of protein (50%) and carbohydrate (30—40%). 

The initial step in the viral life cycle is the attachment of virus particles to the cell surface. Attachment is mediated by binding of the virus to a receptor. Sometimes co-receptors are also involved that might promote post-attachment events in the entry process. Receptor molecules are crmstituents of the cell membrane, and the receptor determinant, the stmcture to which the virus binds, may be either a protein epitope or the carbohydrate of a glycoprotein or a glycolipid. Soluble proteins present in body fluids and in mucus oti respiratory and enteric epithelia may also contain such carbohydrates and therefore interfere with virus binding to the cell siuface. 

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. 

In general, virus receptors carry out normal functions in the cell. For example, in bacteria some phage receptors are pili or flagella, others are cell-envelope components, and others are transport binding proteins. The receptor for influenza vims is a glycoprotein found on red blood cells and on cells of the mucous membrane of susceptible animals, whereas the receptor site of poliovirus is a lipoprotein. However, many animal and plant viruses do not have specific attachment sites at all and the vims enters passively as a result of phagocytosis or some other endocytotic process. 

Infection of CD4+ cells commences via interaction between gp 120 and the CD4 glycoprotein, which effectively acts as the viral receptor. Entry of the virus into the cell, which appears to require some additional cellular components, occurs via endocytosis and/or fusion of the viral and cellular membranes. The gp 41 transmembrane protein plays an essential role in this process. 

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-... 

Non-enveloped viruses generally use the first two penetration mechanisms, while the enveloped viruses enter a cell by endocytosis followed by binding with the membrane of an endosome. In addition to this mechanism, the enveloped viruses fuse directly with the cell membrane. The fusion of the viral envelope with the cell membrane requires the interaction of the glycoproteins of the virus with a cell receptor. After the internalization of the viral particle, the genome is freed for later expression. This process is known as unwrapping and it involves both cellular and viral enzymes. 

As mentioned in Section 17.2.1, HA is a spike glycoprotein anchored to the virus lipid membrane [50], This glycoprotein functions as a receptor-binding protein and is responsible for the first step of viral infection when it binds to sialic acid residues of receptor glycoproteins on host cells [18]. When the virus is endocytosed into the cell, the low pH (5-6) changes the structure of HA, and this new fusion-active state triggers the fusion of the viral membrane and the endosome membrane, ultimately allowing entry of the viral nucleocapsid into the cytosol of the host cell [18]. 

In addition to the lipid bilayer, enveloped viruses generally have two or more distinct layers of protein that are organized across the membrane. Thus, most viruses have an outer layer of proteins, usually glycoproteins, which are anchored in the membrane as integral membrane proteins. These proteins function to attach the virion to target host cell receptors and facilitate the entry or fusion of the viral membrane with that of the host cell. In addition, some viruses also contain enzymatic activities associated with this outer layer of protein. For example, influenza virus carries with it a neuraminidase that is responsible for cleaving sialic acid residues on host cells. 

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