Paramyxovirus fusion

Negative-strand RNA viruses, 158-163 ebola virus matrix protein/ glycoprotein, 162-163 hemagglutinin-neuraminidase and, 162 influenza A and, 158-163 Ml and, 161 Ms and, 161-162 neuraminidase and, 161 paramyxovirus fusion protein and, 162 Neuraminidase, negative-strand RNA viruses and, 161... 

Paramyxovirus fusion protein, negative-strand RNA viruses and, 162 Pariacoto virus, 223 Particle reconstruction images, 198 Parvoviridae family, 238-240 Desovirinae subfamily of 239 Parvovirinae subfamily of 239 of single-stranded DNA (ssDNA) viruses, 242... 

Inhibitors of Protein-Protein Interactions in Paramyxovirus Fusion A Focus on Respiratory Syncytial Virus... 

Many enveloped viruses share a common mechanism of fusion, mediated by a virus-encoded glycoprotein that contains heptad repeats in its extraceUnlar domain. Dnring the fnsion process, these domains rearrange to form highly structured and thermodynamically stable coiled-coils. Viruses encoding fusion proteins that have these domains inclnde members of the paramyxovirus family (e.g., respiratory syncytial virus, metapneumovirus, and measles virus), ebola virus, influenza, and members of the retroviridae (e.g., human T cell lenkemia virus type-1 and human immunodeficiency virus type-1, HlV-1). Peptide inhibitors of fusion that disrupt the... 

Binding to the cell surface proceeds at 0°C, but the cells are not infected (Helenius et al., 1980). When the cells are warmed to 37 C the virus is rapidly removed from the cell surface and infection ensues. In general there are two ways to envisage the entry of enveloped viruses into cells—either by penetration directly through the plasma membrane, or by endocytosis (engulfment by a plasma membrane-derived vesicle) (see Lonberg-Holm and Philipson, 1974). In both cases delivery of the nucleocapsid with the RNA would have to involve a fusion reaction between the viral envelope and either the cell surface membrane or the vesicle membrane. Paramyxoviruses are known to fuse their envelopes with the plasma membrane (see Hosaka and Shimizu, 1977). However, whether this process leads to productive infection has not yet been settled. 

Paramyxoviruses cause respiratory tract diseases such as croup and pneumonia, as well as measles and mumps. The envelope proteins of these viruses share some features in common with influenza and retroviruses. These similarities include a precursor protein that is cleaved into two fragments, the second of which, called El, bears a fusion peptide at its amino terminus. In addition, peptides from the paramyxovirus FI proteins assemble into stable helical bundles resembling HIV gp41 and influenza HA2 (Baker et al, 1999 Lawless-Delmedico et al, 2000 Zhao et al, 2000). The paramyxovirus F protein differs from influenza HA and retroviral TM... 

The authors of the NDV-F structure propose that they have crystallized a mixture of the native and sprung forms of the spike protein, and that these two versions are similar enough structurally to pack into the same crystal lattice (Chen et al., 2001a). In light of the enormous structural changes that are observed on exposure of influenza HA to low pH, the possibility that minimal conformational changes occur in paramyxoviruses is remarkable. Furthermore, the long central helix of NDV-F is proposed to point in the opposite direction from that of influenza HA, such that extension of the central coiled coil sends the fusion peptides in the direction of the virus membrane (Fig. 12). 

Although there are mechanistic differences between retroviruses, paramyxoviruses, and the orthomyxovirus influenza, the viruses discussed to this point have definite structural and functional similarities including spikelike, trimeric native structures and the presence of coiled coils in their fusion-active subunits. The flaviviruses and alphaviruses, however, appear to be another class of enveloped viruses entirely. Flaviviruses include yellow fever. West Nile virus. Dengue virus, and tick-borne encephalitis virus (TBEV). Alphaviruses, of the togavirus family, include... 

Animal V. pass through the cell membrane, either by fusion (e.g. enveloped paramyxoviruses) or by en-dot osis (e.g. Semliki Forest vims). Fusion the vims bin to the cell receptor, the viral envelope and the cell membrane become perforated, the two membranes seal together, and the capsid enters the cell. Endocytosis following adsorption of the vims, a depression forms on the cell surface in the receptor region (adsorption site). Continued invagination forms a coated pit (lined on the cytoplasmic side with cla-thrin), eventually enclosing the vims in a vesicle, which is finally released into the interior of the host cell by abstriction, still surrounded by the vesicle membrane the latter loses its clathrin coat and fuses with other cellular vesicles to form vesicles called en-dosomes viral and endosomal membranes then fuse and the nucleocapsld is released into the host cytoplasm. 

It has been known for some time that different viruses have different effects on cell membranes. In particular, the enveloped viruses can cause early cell fusion as they enter the host cell or late cell fusion after replication of the virus. These phenomena apply particularly to the paramyxoviruses and have been dubbed fusion from without and fusion from within (Bratt and Gallaher, 1969). Other enveloped viruses can produce similar but usually less striking effects on cell fusion. Nonenveloped viruses can also cause drastic changes in cell membranes, usually resulting in alteration in the permeability barrier of the cell membrane. Still other viruses, or the same viruses under different conditions, can alter in a more subtle way the active or passive transport mechanisms of cells. Under some conditions, some viruses even stimulate the formation of cell membranes by inducing augmented synthesis of cellular membrane lipids. 

The membranes of negative-strand viruses lacking an identifiable fusion factor can also fuse with interacting cell membranes but to a much lesser extent than the paramyxoviruses. Influenza A and B... 

The paramyxoviruses, largely because of their profound cell-fusing activity, have served as an important model of membrane perturbation by viruses. During Sendai virus-mediated fusion of mouse ascites cells, Pasternak and Micklem (1973) detected loss of intracellular metabolites coincident with inhibition of their accumulation from the medium. This failure to maintain selective permeability did not occur at 0°C and was unaffected by cytochalasin B which inhibits fusion by the virus. Chick embryo fibroblasts infected with Newcastle disease virus were found to release cellular enzymes, such as lactate dehydrogenase, glutamic oxaloacetic transaminase, and lysosomal enzymes (Katzman and Wilson, 1974). These cells also became... 

Scheid, A., and Choppin, P. W., 1974, Identification of biological activities of paramyxovirus glycoproteins. Activation of cell fusion, hemolysis and infectivity by proteolytic cleavage of an inactive precursor protein of Sendai virus. Virology 57 475. 

Fusion peptide of the paramyxovirus PIV5 POPC/POPG, DOPC/DOPG, and DOPE 133... 

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