Virus necrosis

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. 

Very few self-sufficient viruses have only 60 protein chains in their shells. The satellite viruses do not themselves encode all of the functions required for their replication and are therefore not self-sufficient. The first satellite virus to be discovered, satellite tobacco necrosis virus, which is also one of the smallest known with a diameter of 180 A, has a protein shell of 60 subunits. This virus cannot replicate on its own inside a tobacco cell but needs a helper virus, tobacco necrosis virus, to supply the functions it does not encode. The RNA genome of the satellite virus has only 1120 nucleotides, which code for the viral coat protein of 195 amino acids but no other protein. With this minimal genome the satellite viruses are obligate parasites of the viruses that parasitize cells. 

Figure 16.S Schematic illustration of the way the 60 protein subunits are arranged around the shell of safellite tobacco necrosis virus. Each subunit is shown as an asymmetric A. The view is along one of the threefold axes, as in Figure 16.3a. (a) Three subunifs are positioned on one triangular tile of an Icosahedron, in a similar way to that shown in 16.4a. The red lines represent a different way to divide the surface of the icosahedron into 60 asymmetric units. This representation will be used in the following diagrams because it is easier to see the symmetry relations when there are more than 60 subunits in the shells, (b) All subunits are shown on the surface of the virus, seen in the same orientation as 16.4a. The shell has been subdivided into 60 asymmetric units by the red lines. When the corners are joined to the center of the virus, the particle is divided into 60 triangular wedges, each comprising an asymmetric unit of the virus. In satellite tobacco necrosis virus each such unit contains one polypeptide chain...

The size of this viral particle is of course larger than that of a virus with only 60 subunits. The diameter of tomato bushy stunt virus is 330 A compared with 180 A for satellite tobacco necrosis virus. The increase in volume of the capsid means that a roughly four times larger RNA molecule can be accommodated. 

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. 

Figure 16.14 Schematic diagrams of three different viral coat proteins, viewed in approximately the same direction. Beta strands I through 8 form the common jelly roll barrel core, (a) Satellite tobacco necrosis virus coat protein, (b) Subunit VPl from poliovirus.

Satellite tobacco necrosis virus is an example of a T = 1 virus structure. The 60 identical subunits interact tightly around the fivefold axes on the surface of the shell and around the threefold axes on the inside. These interactions form a scaffold that links all subunits together to complete the shell. 

Jones, T.A., Liljas, L. Structure of satellite tobacco necrosis virus after crystallographic refinement at 2.5 A resolution. /. Mol. Biol. 177 735-768, 1984. 

Extensive investigations have been performed related to the synthesis of new adamantane derivatives with better therapeutic actions and less adverse effects. For example, it has been proved that adamantylamino-pyrimidines and -pyridines are strong stimulants of mmor necrosis factor-a (TNF-a) [132]. TNF is a substance that can improve the body s namral response to cancer by killing cancer cells. Another example is 1,6-diaminodiamantane [87], which possesses an antitumor and antibacterial activity. Also, many derivatives of aminoadamantanes have antiviral activity like 3-(2-adamantyl) pyrolidines with two pharmacophoric amine groups, which have antiviral activity against influenza-A virus [133]. 

Koka P, He K, Zack JA, Kitchen S, Peacock W, Fried 1, Tran T, Yashar SS, MerrUl JE (1995) Human immunodeficiency virus 1 envelope proteins induce interleukin 1, tumor necrosis factor alpha, and nitric oxide in glial cultures derived from fetal, neonatal, and adult human brain. J Exp Med 182 941-951... 

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... 

M. Maurhofer, C. Hase, P. Meuwly, J. P. Metraus, and G. Defago, Induction of systemic resistance of tobacco necrosis virus by the root colonizing Pseudomonas fluorescens strain CHAO Influence of the gacA gene and of pyoverdine production. Phytopathology 54 139 (1994). 

Yee, L. J. et al., Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection, Genes Immun., 1, 386, 2000. 

Spitzbergen, J.M. et al., Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or Aroclor 1254 on the resistance of rainbow trout, Salmo gairdneri R, to infectious haematopoietic necrosis virus, J. Fish Dis., 11,73, 1986. 

Note IL2, interluekin 2 HER2, human epidermal growth factor receptor 2 RSV, respiratory syncytial virus TNF, tumor necrosis factor IgE, Immunoglobulin E EGER, epidermal growth factor receptor VEGF, vascular endothelial growth factor. 

Brown, K. D., B. S. Hostagee, and G. A. Bishop, Differential signaling and tumor necrosis factor receptor-associated factor (TRAP) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMPl)./ Exp Med, 2001, 193(8), 943-54. 

Anti-hepatitis B virus activity in vitro and in vivo was also found in wogonin and baicalein (Fig. 4), the major active constituents of the traditional Chinese medicine Scutellaria radix.More recently, Blach-Olszewska et al investigated the effect of baicalein and wogonin on two important mechanisms of innate immunity The secretion of cytokines, and the natural resistance of human leukocytes to viral infection. The results obtained indicate that these fiavonoids modulate cytokine production, that is they inhibit interferons-a and -y, and stimulate tumor necrosis factor-a and interleukin production. They also augment the resistance of peripheral blood leukocytes to the vesicular stomatitis virus. 

Crowfoot, D. and Schmidt, G. M. J. (1945). X-ray crystallographic measurements on a single crystal of a tobacco necrosis virus derivative. Nature 155,504-505. 

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