Nucleocapsid

Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, Kramer T, Niewohner U, Pleiss U, Stoltefuss J et al. (2003) Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 299 893-896 Ehon GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ (1977) Selectivity of action of an antiherpetic agent, 9-(2-hydroxy ethoxy methyl) guanine, Proc Natl Acad Sci USA 74 5716-5720... 

Since our original aPNA publication, there have been other reports of the incorporation of nucleobases into a-helical peptides. Mihara and coworkers reported that a-hehcal coiled-coiled peptides could be stabilized by base pairs between complementary y-nucleobase-a-aminobutanoic acids [78] They have also reported that the incorporation of such nucleoamino acids into a-hehcal segments of HIV-1 Rev and HIV-1 nucleocapsid protein can result in increased binding affinity and specificity to HIV-1 RRE RNA and SL3 RNA respectively [79, 80]. 

Alee TM, Popik W (2004) APOBEC3G is incorporated into virus-hke particles by a direct interaction with HIV-1 Gag nucleocapsid protein. J Biol Chem 279(33) 34083-34086... 

Hepatitis viruses Hepatitis B virus (HBV) Spherical enveloped particle 42 nm in diameter enclosing an inner icosahedral 27-nm nucleocapsid In areas such as South-East Asia and Africa, most children are infected by perinatal transmission. In the Western world the virus is spread through contact with contaminated blood or by sexual intercourse. There is strong evidence that chronic infections with HBV can progress to liver cancer... 

Filoviruses Ebola virus Long filamentous rods composed of a lipid envelope surrounding a helical nucleocapsid lOOOnm long, 80nm in diameter The virus is widespread amongst populations of monkeys. It can be spread to humans by contact with body fluids from the primates. The resulting haemorragic fever has a 90% case fatality rate... 

All enveloped human vimses acquire their phospholipid coating by budding through cellular membranes. The maturation and release of enveloped influenza particles is illustrated in Fig. 3.8. The capsid protein subunits are transported flom 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 fiom 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 flxm the cell. Vims particles are released in this way over a period of hours before the cell eventually dies. 

Hepatitis B is diagnosed when HBsAg is detectable in the serum. The nucleocapsid of the HBsAg contains the core protein that produces HBcAg, which is undetectable in the serum. The presence of antibodies against anti-HBc to IgM indicates active infection, and anti-HBc to IgG relates to either chronic infection or possible immunity against HBV. 

The complete complex of nucleic acid and protein, packaged in the virus particle, is called the virus nucleocapsid. Although the virus structure just described is frequently the total structure of a virus particle, a number of animal viruses (and a few bacterial viruses) have more complex structures. These viruses are enveloped viruses, in which the nucleocapsid is enclosed in a membrane. Virus membranes are generally lipid bilayer membranes, but associated with these membranes are often virus-specific proteins. Inside the virion are often one or more virus-specific enzymes. Such enzymes usually play roles during the infection and replication process. 

Virus symmetry The nucleocapsids of viruses are constructed in highly symmetrical ways. Symmetry refers to the way in which the protein morphological units are arranged in the virus shell. When a symmetrical structure is rotated around an axis, the same form is seen again after a certain number of degrees of rotation. Two kinds of symmetry are recognized in viruses which correspond to the two primary shapes, rod and spherical. Rod-shaped viruses have helical symmetry and spherical viruses have icosahedral symmetry. 

Enveloped viruses Many viruses have complex membranous structures surrounding the nucleocapsid. Enveloped viruses are common in the animal world (for example, influenza virus), but some enveloped bacterial viruses are also known. The virus envelope consists of a lipid bilayer with proteins, usually glycoproteins, embedded in it. Although the glycoproteins of the virus membrane are encoded by the virus, the lipids are derived from the membranes of the host cell. The symmetry of enveloped viruses is expressed not in terms of the virion as a whole but in terms of the nucleocapsid present inside the virus membrane. 

Figure 5.29 Uptake of an enveloped virus particle by an animal cell, (a) The process by which the viral nucleocapsid is separated from its envelope, (b) Electron micrograph of adenovinis panicles entering a cell. Each panicle is about 70 nm in diameter.

Ramanathan, H.N., Chung, D.-H., Plane, S.J., Sztul, E., Chu, Y.-K., Gutderi, M.C., McDowell, M., Ali, G., and Jonsson, C.B. (2007) Dynein-dependent transport of the Hantaan virus nucleocapsid protein to the endoplasmic reticulum-golgi intermediate compartment./. Virol. 81, 8634-8647. 

Figure 6. Structure of a HIV vilion with envelope glycoproteins and nucleocapside proteins. Magnified wire structure of its glysoprotein gp120 shows V3 and V4 loops with S-S bonding sites.

Figure 8. Primary structure of the nucleocapsid protein p7 with the two zinc fingers.

Greiff [3.25] classified the virus into five categories 1, Nucleic acid type (either DNA-core or RNA-core) 2, sensitivity against lipid solvents 3, envelope about the nucleocapsid or not (naked) 4, pH sensitivity, exposure to pH 3 for 30 min differentiates between those viruses, which lose more than a decade in titer and those which lose no titer or less than one decade 5, heat-sensitive virus cannot be exposed to +50 °C for 30 min. 

The nucleocapsid of the C. sonorensis polydnavirus is prolate ellipsoid in shape and has two envelopes (37) one envelope is obtained in the nucleus and the other as the virus buds through the calyx cell membrane... 

Maynard, A. T., Huang, M., Rice, W. G., and Covell, D. G. 1998. Reactivity of the HIV-1 nucleocapsid protein p7 zinc finger domains from the perspective of density-functional theory. Proc. Natl. Acad. Sci. USA 95 11578-11583. 

Zinc-finger proteins are also possible targets for bicyclams. All nu-cleocapsid proteins of known strains of retroviruses contain one or two copies of an invariant sequence, Cys-X2-Cys-X4-His-X4-Cys. Proteins with this sequence bind zinc stoichiometrically with dissociation constants of ca. 10-12M (377). Under physiological conditions, a 10-fold excess of EDTA removes only 50% of zinc from the zinc finger domain of HIV-1 nucleocapsid protein (378). 

An alternative method for removing Zn from the active site of zinc proteins is to use aromatic nitroso compounds such as 3-nitrosoben-zamide and 6-nitroso-l,2-benzopyrone (382). These agents can oxidize Zn-bound cysteine S and can inhibit HIV-1 infection in human lymphocytes. They also eject zinc from isolated HIV-1 nucleocapsid zinc-fingers and from intact HIV-1 virions. 

As it is the outer surface of the virus particle, whether nucleocapsid or envelope, that first makes contact with the membrane of the host cell, its structure and properties are of vital importance in understanding the process of infection. In general, naked (envelope-free) viruses are resistant and survive well in the outside world they may also be bile-resistant, allowing infection through the alimentary canal. Enveloped viruses are more susceptible to environmental factors such as drying, gastric acidity, and bile. These differences in susceptibility influence the ways in which these viruses can be transmitted. 

Adsorption (Binding). The process of adsorption by a host cell depends first upon the operation of general intermolecular forces, then upon more specific interactions between the molecules of the nucleocapsid or the virus membrane and the molecules of the host cell membrane. In most cases there has... 

The mechanism of zinc deprivation by 3-nitrosobenzamide was elucidated most recently. When the reconstituted nucleocapsid protein p7 of HIV-1 (15 i-M) was incubated with 3-nitrosobenzamide (300 iM) at pH 7.5, three disulfide bonds per protein molecule were formed while 3-nitrosobenzamide was reduced to the hydroxylamine. Molecular masses of p7 adducts augmented by one or two 3-nitrosobenzamide residues were observed by electrospray ionization MS, consistent with covalent bond formation between cysteine sulfur and the nitroso nitrogen atom127. 

C2HC Zn finger (smart00343) KCYNCGKPGHIARDC PS Found in the Nucleocapsid protein of retrovirus. Also found in eukaryotic RNA-or ssDNA-binding proteins Human Rb-BP 6 (NP 008841)-retmoblatoma-binding protein 6 378, 379... 

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