Viruses Spherical

Flaviviruses Yeiiow fever virus Spherical particles 40 nm in diameter with an inner core surrounded by an adherent lipid envelope The virus is spread to humans by mosquito bites the liver is the main target necrosis of hepatocytes leads to jaundice and fever... 

Flaviviruses Yellow fever virus Spherical particles 40 nm in diameterwith an inner core surrounded by an adherent lipid envelope... 

A nucleic acid can never code for a single protein molecule that is big enough to enclose and protect it. Therefore, the protein shell of viruses is built up from many copies of one or a few polypeptide chains. The simplest viruses have just one type of capsid polypeptide chain, which forms either a rod-shaped or a roughly spherical shell around the nucleic acid. The simplest such viruses whose three-dimensional structures are known are plant and insect viruses the rod-shaped tobacco mosaic virus, the spherical satellite tobacco necrosis virus, tomato bushy stunt virus, southern bean mosaic vims. 

In this chapter we will examine the construction principles of spherical viruses, the structures of individual subunits and the host cell binding properties of the surface of one of the picornaviruses, the common cold virus. 

The protein shells of spherical viruses have icosahedral symmetry... 

Two basic principles govern the arrangement of protein subunits within the shells of spherical viruses. The first is specificity subunits must recognize each other with precision to form an exact interface of noncovalent interactions because virus particles assemble spontaneously from their individual components. The second principle is genetic economy the shell is built up from many copies of a few kinds of subunits. These principles together imply symmetry specific, repeated bonding patterns of identical building blocks lead to a symmetric final structure. 

Figure 16.2 The icosahedron (top) and dodecahedron (bottom) have identical symmetries but different shapes. Protein subunits of spherical viruses form a coat around the nucleic acid with the same symmetry arrangement as these geometrical objects. Electron micrographs of these viruses have shown that their shapes are often well represented by icosahedra. One each of the twofold, threefold, and fivefold symmetry axes is indicated by an ellipse, triangle, and pentagon, respectively.

The asymmetric unit of an icosahedron can contain one or several polypeptide chains. The protein shell of a spherical virus with icosahedral symmetry... 

Complex spherical viruses have more than one polypeptide chain in the asymmetric unit... 

The molecular basis for quasi-equivalent packing was revealed by the very first structure determination to high resolution of a spherical virus, tomato bushy stunt virus. The structure of this T = 3 virus was determined to 2.9 A resolution in 1978 by Stephen Harrison and co-workers at Harvard University. The virus shell contains 180 chemically identical polypeptide chains, each of 386 amino acid residues. Each polypeptide chain folds into distinct modules an internal domain R that is disordered in the structure, a region (a) that connects R with the S domain that forms the viral shell, and, finally, a domain P that projects out from the surface. The S and P domains are joined by a hinge region (Figure 16.8). 

The fact that spherical plant viruses and some small single-stranded RNA animal viruses build their icosahedral shells using essentially similar asymmetric units raises the possibility that they have a common evolutionary ancestor. The folding of the main chain in the protein subunits of these viruses supports this notion. 

The coat proteins of many different spherical plant and animal viruses have similar jelly roll barrel structures, indicating an evolutionary relationship... 

One of the most striking results that has emerged from the high-resolution crystallographic studies of these icosahedral viruses is that their coat proteins have the same basic core structure, that of a jelly roll barrel, which was discussed in Chapter 5. This is true of plant, insect, and mammalian viruses. In the case of the picornaviruses, VPl, VP2, and VP3 all have the same jelly roll structure as the subunits of satellite tobacco necrosis virus, tomato bushy stunt virus, and the other T = 3 plant viruses. Not every spherical virus has subunit structures of the jelly roll type. As we will see, the subunits of the RNA bacteriophage, MS2, and those of alphavirus cores have quite different structures, although they do form regular icosahedral shells. 

The cleft where this drug binds is inside the jelly roll barrel of subunit VPl. Most spherical viruses of known structure have the tip of one type of subunit close to the fivefold symmetry axes (Figure 16.15a). In all the picor-naviruses this position is, as we have described, occupied by the VPl subunit. Two of the four loop regions at the tip are considerably longer in VPl than in the other viral coat proteins. These long loops at the tips of VPl subunits protrude from the surface of the virus shell around its 12 fivefold axes (Figure 16.15b). 

The structures of many different plant, insect, and animal spherical viruses have now been determined to high resolution, and in most of them the subunit structures have the same jelly roll topology. However, a very different fold of the subunit was found in bacteriophage MS2, whose structure was determined to 3 A resolution by Karin Valegard in the laboratory of Lars Liljas, Uppsala. 

Small spherical viruses have a protein shell around their nucleic acid that is constructed according to icosahedral symmetry. Objects with icosahedral symmetry have 60 identical units related by fivefold, threefold, and twofold symmetry axes. Each such unit can accommodate one or severed polypeptide chains. Hence, virus shells are built up from multiples of 60 polypeptide chains. To preserve quasi-equivalent symmetry when packing subunits into the shell, only certain multiples (T = 1, 3, 4, 7...) are allowed. 

Harrison, S.C. Multiple modes of subunit association in the structures of simple spherical viruses. Trends Biochem. Sci. 9 345-351, 1984. 

Chen, Z., et al. Protein-nucleic acid interactions in a spherical virus the structure of beanpod mottle virus at 3.0 A resolution. Science 245 154-159, 1989. 

In order to enhance the stability of hposomes and to provide a biocompatible outermost surface shucture for controlled immobihzation (see Section IV), isolated monomeric and oligomeric S-layer protein from B. coagulans E38/vl [118,123,143], B. sphaericus CCM 2177, and the SbsB from B. stearothermophilus PV72/p2 [119] have been crystallized into the respective lattice type on positively charged liposomes composed of DPPC, HD A, and cholesterol. Such S-layer-coated hposomes are spherical biomimetic structures (Fig. 18) that resemble archaeal ceUs (Fig. 14) or virus envelopes. The crystallization of S-... 

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. 

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... 

Retroviruses Human T-cell leukaemia virus (HTLV-1) Spherical enveloped virus lOOnm in diameter, icosahedral cores contain two copies of linear RNA molecules and reverse transcriptase HTI.V is spread inside infected lymphocytes in blood, semen or breast milk. Most infections remain asymptomatic but after an incubation period of 10-40 years in about 2% of cases, adult T-cell leukaemia can result... 

Three types of particles are associated with FIBV small spherical particles, 22 nm in diameter tubular particles, also having a diameter of 22 nm and larger spherical particles (42 nm diameter) known as the Dane particles. The Dane particle alone has a typical virus structure and appears to be infectious but is the least common form. It consists of... 

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. 

Of all the fullerene forms, the nearly spherical properties of C o have attracted the greatest attention, especially in the field of bioconjugation. In addition to its physical properties, C o fullerenes have unique photo-optical and electro-chemical properties, which make them useful as carriers for biomedical research applications. For instance, upon exposure to light C o will generate singlet oxygen, which can be used in vivo to cleave biological molecules, particularly DNA and RNA. Studies indicate that irradiation of Cgo in solution can be used to destroy virus contamination (Kasermann and Kempf, 1997). Solutions of Buckminsterfullerene are a deep purple color, whereas other sizes of fullerenes display a variety of other colors. 

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