Virus particles structures

S-TT Klug, A., The tobacco mosaic virus particle structure and assembly , Phil. Trans. RoyalSoc. Ser. B, Biol. Scl. 1999, 354, 531-535. 

Stubbs, G. (1999). Tobacco mosaic virus particle structure and the initiation of disassembly. Philos. Trans. R. Soc. Lond. B Biol. Sci. 354, 551-557. 

Klug, A. The tobacco mosaic virus particle Structure and... 

The viral products most commonly implicated in shut-off in many virus-cell systems have been structural components of the virus particles. Structural components of adenovirus (Pereira, 1960), frog virus-3 (Maes and Granoff, 1967), vesicular stomatitis virus (Baxt and Bablanian, 1976), herpesvirus type 1 (Fenwick and Walker, 1978), and vaccinia virus (Moss, 1968) have been implicated as the agents responsible for inhibition of host protein synthesis. 

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. 

As examples of such quasi-equivalent arrangement of subunits, we will examine the T = 3 and T = 4 packing modes, both of which are found in known virus particles. In the T = 3 structure, which has 180 subunits (3 x 60),... 

Rossmann suggested that the canyons form the binding site for the rhi-novirus receptor on the surface of the host cells. The receptor for the major group of rhinoviruses is an adhesion protein known as lCAM-1. Cryoelectron microscopic studies have since shown that ICAM-1 indeed binds at the canyon site. Such electron micrographs of single virus particles have a low resolution and details are not visible. However, it is possible to model components, whose structure is known to high resolution, into the electron microscope pictures and in this way obtain rather detailed information, an approach pioneered in studies of muscle proteins as described in Chapter 14. 

Figure 16.23 Overview of the structure of the SV40 virus particle, showing the packing of pentamers. The subunits of pentamers on fivefold positions are shown in white those of pentamers in six-coordinated positions are shown in colors. The six colors indicate six quite different environments for the subunit. (Courtesy of S. Harrison.)...

Moulds and yeasts show varying responses to biocides. These organisms are often important in the pharmaceutical context because they may cause spoilage of formulated products. Various types of protozoa are potentially pathogenic and inactivation by biocides may be problematic. Viral response to biocides depends upon the type and structure of the virus particle and on the nature of the biocide. 

Hepatitis B surface antigen Monomer has 226 amino acids Yeast Mammalian cells Vaccination Approved for sale Monomer self-assembles into structure resembling virus particles... 

In another rather different application, ROA data indicated that the coat protein subunits of intact tobacco rattle virus contain a significant amount of PPII structure, which is possibly associated with sequences previously suggested to be mobile and to be exposed externally in the intact virus particle and which may be associated with its transmission by nematodes (Blanch et al., 2001b). 

The structures of virions (virus particles) are quite diverse. Viruses vary widely in size, shape, and chemical composition. The... 

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. 

Figure 5.4 Structure and manner of assembly of a simple virus, tobacco mosaic virus, (a) Electron micrograph at high resolution of a portion of the virus particle, (b) Assembly of the tobacco mosaic virion. The RNA assumes a helical configuration surrounded by the protein capsomeres. The center of the particle is hollow.

In all cases, the characteristic structure of the virus is determined by the structure of the protein subunits of which it is constructed. Self-assembly leads to the final virus particle. 

What is the function of the membrane in a virus particle We will discuss this in detail later but note that because of its location in the virion, the membrane is the structural component of the virus particle that interacts first with the cell. The specificity of virus infection, and some aspects of virus penetration, are controlled in part by characteristics of virus membranes. 

Complex viruses Some virions are even more complex, being composed of several separate parts, with separate shapes and symmetries. The most complicated viruses in terms of structure are some of the bacterial viruses, which possess not only icosahedral heads but helical tails. In some bacterial viruses, such as the T4 virus of Escherichia coli, the tail itself is a complex structure. For instance, T4 has almost 20 separate proteins in the tail, and the T4 head has several more proteins. In such complex viruses, assembly is also complex. For instance, in T4 the complete tail is formed as a subassembly, and then the tail is added to the DNA-containing head. Finally, tail fibers formed from another protein are added to make the mature, infectious virus particle. 

The basic problem of virus replication can be simply put the virus must somehow induce a living host cell to synthesize all of the essential components needed to make more virus particles. These components must then be assembled into the proper structure and the new virus particles must escape from the cell and infect other cells. The various phases of this replication process in a bacteriophage can be categorized in seven steps ... 

The bacterial RNA viruses are all of quite small size, about 26 nm in size, and they are all icosahedral, with 180 copies of coat protein per virus particle. The complete nucleotide sequence of several RNA phages are known. In the RNA phage MS2, which infects Escherichia coli, the viral RNA is 3,569 nucleotides long. The virus RNA, although single stranded, has extensive regions of secondary and tertiary structure. The RNA strand in the virion has the plus (+) sense, acting directly as mRNA upon entry into the cell. 

The virus particle of phage T4 is structurally complex. It consists of an icosahedral head which is elongated by the addition of one or two extra bands of protein hexamers, the overall dimensions of the... 

Completely different mechanisms are involved in the self-assembly of the tobacco mosaic virus (TMV). This virus consists of single-strand RNA, which is surrounded by 2,130 identical protein units, each of which consists of 158 amino acid residues. A virus particle, which requires the tobacco plant as a host, has a rodlike structure with helical symmetry ( Stanley needles ). It is 300 nm long, with a diameter of 18nm. The protein and RNA fractions can be separated, and the viral... 

For example, with the crystal structure of the aspartyl protease from human immundeficiency virus (HIV-1) in 1989 came the opportunity to design molecules to block this important enzyme that acts as a molecular scissors. HIV is the virus responsible for AIDS. Essential to viral replication, the HIV protease cuts long strands composed of many proteins into the functional proteins found in mature virus particles. This proteolysis occurs at the very end of the HIV replication cycle (Figure 7-1). The three-dimensional structural information derived from the x-ray crystal structure, combined with computer modeling techniques, allowed chemists to design potent, selective inhibitors of the protease enzyme (Figure... 

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. 

One of the most intriguing recent examples of disordered structure is in tomato bushy stunt virus (Harrison et ah, 1978), where at least 33 N-terminal residues from subunit types A and B, and probably an additional 50 or 60 N-terminal residues from all three subunit types (as judged from the molecular weight), project into the central cavity of the virus particle and are completely invisible in the electron density map, as is the RNA inside. Neutron scattering (Chauvin et ah, 1978) shows an inner shell of protein separated from the main coat by a 30-A shell containing mainly RNA. The most likely presumption is that the N-terminal arms interact with the RNA, probably in a quite definite local conformation, but that they are flexibly hinged and can take up many different orientations relative to the 180 subunits forming the outer shell of the virus particle. The disorder of the arms is a necessary condition for their specific interaction with the RNA, which cannot pack with the icosahedral symmetry of the protein coat subunits. 

As an example, consider the genome of the hepatitis C virus. The genome codes for a single polyprotein that contains about 3010 amino acids. The polyprotein is subsequently cleaved into at least 10 proteins, including several which are structural components of the virus particle and several which are required, in one way or another, for the process of replication of the viral RNA or cleavage of the polyprotein itself into its functional units. 

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