Viruses, nucleic acids and

Caspar, D. L. D. Klug, A. 1963 Structure and assembly of regular virus particles. In Viruses, nucleic acids, and cancer, pp. 27-39. Baltimore Williams Wilkins. 

The methods used in the recovery, extraction, and purification must be described in detail. Special attention must be paid to the elimination of viruses, nucleic acids, and undesirable antigenic materials. 

Use As an anion exchanger in chromatography. It is less basic than DEAE-cellulose and serves to separate viruses, nucleic acids, and nucleoproteins. 

Yarmolinsky, M. In Viruses, Nucleic Acids, and Cancer, p. 151. Baltimore Williams and Wilkins Co. 1963. 

From a variety of sources information has been amassed that virus nucleic acid and protein synthesis take place independently with regard to time and the nitrogenous precursors (1) Cohen (56,57) finds that protein synthesis goes on from the beginning of infection but DNA formation is initiated only after a lag of about 10 to 12 minutes. (2) Indirect evidence from study of the effects of inhibitors such as proflavine and mustard gas and of radiation sensitivity suggests that DNA formation... 

Wilson, H.R. Diffraction of X-rays by Proteins, Nucleic Acids and Viruses. London Edward Arnold, 1966. 

Vibrio (i) Curved, rod-shaped bacterial cell, (ii) Bacterium of the genus Vibrio. Virion Virus particle the virus nucleic acid surrounded by protein coat and in some cases other material. 

FIGURE 1.25 The virus life cycle. Viruses are mobile bits of genetic iuformatiou encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viral-specific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease. 

Heat is the most reliable method of virus disinfection. Most human pathogenic viruses are inactivated following exposure at 60°C for 30 minutes. The virus of serum hepatitis can, however, survive this temperature for up to 4 hours. Viruses are stable at low temperatures and are routinely stored at -40 to -70°C. Some viruses are rapidly inactivated by drying, others survive well in a desiccated state. Ultraviolet light inactivates viruses by damaging their nucleic acid and has been used to prepare viral vaccines. These facts must be taken into account in the storage and preparation of viral vaccines (Chapter 15). 

Since nucleic acids and enzymes play such a large role in chromosome replication during mitosis, a considerable amount of research has been conducted in this area to control viruses. On the molecular level, analogues of nucleic acids are capable of forming complexes with adenine, cytosine, uracil, thymine, and guanine. Through complexation, these nucleic acid analogues are potential inhibitors of biosyntheses that require nucleic acids as templates. 

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. 

Assembly of nucleic acid and protein subunits (and membrane components in enveloped viruses) into new virus particles ... 

As we have noted, the outcome of a virus infection is the synthesis of viral nucleic acid and viral protein coats. In effect, the virus takes over the biosynthetic machinery of the host and uses it for its own synthesis. A few enzymes needed for virus replication may be present in the virus particle and may be introduced into the cell during the infection process, but the host supplies everything else energy-generating system, ribosomes, amino-acid activating enzymes, transfer RNA (with a few exceptions), and all soluble factors. The virus genome codes for all new proteins. Such proteins would include the coat protein subunits (of which there are generally more than one kind) plus any new virus-specific enzymes. 

Virus infection obviously upsets the regulatory mechanisms of the host, since there is a marked overproduction of nucleic acid and protein in the infected cell. In some cases, virus infection causes a complete shutdown of host macromolecular synthesis while in other cases host synthesis proceeds concurrently with virus synthesis. In either case, the regulation of virus synthesis is under the control of the virus rather than the host. There are several elements of this control which are similar to the host regulatory mechanisms, but there are also some uniquely viral regulatory mechanisms. We discuss various regulatory mechanisms when we consider the individual viruses later in this chapter. 

It should already be clear from what has been stated that a great diversity of viruses exist. It should therefore not be surprising that there is also a great diversity in the manner by which virus multiplication occurs. Interestingly, many viruses have special features of their nucleic acid and protein synthesis processes that are not found in cells. In the present chapter, we are only able to present some of the major types of virus replication patterns, and must skip some of the interesting exceptional cases. 

The Li+-induced inhibition of the production of the HSV virus may be related to its actions upon viral DNA polymerase production and activity. Li+ reduces both the synthesis of DNA polymerase in tissue culture and the activity of DNA polymerase in vitro, each by about 50%. It has been proposed that Li+ reduces the biosynthesis of viral polypeptides and nucleic acids, and hence inhibits viral DNA replication by competition with Mg2+, a cofactor of many enzymes [243]. However, the inhibitory effect of Li+ on HSV replication in tissue culture is not affected by Mg2+ levels. A more likely hypothesis is the alteration of the intracellular K+ levels, possibly modifying levels of the high-energy phosphate compounds by replacement of either Na+ or K+ in Na+/K+-ATPase [244]. In tissue culture, HSV replication has been shown to be affected by the... 

Protein, Nucleic Acid, and Viruses, Thermal Effects on... 

Virus in the simplest cases, an infectious aggregate of nucleic acid and protein, lacking both structures and metabolic machinery usually found in cells. 

Some pathogens invade, survive and proliferate within host cells. These include viruses, bacteria and parasites. Viruses are unique since to proliferate they require the nucleic acid and protein synthetic machinery of the infected cells. Hence, once the virus has infected the host cell, the most effective means of killing the virus is to kill the infected cell. Viruses that escape from the dead host cell are neutralised by binding to the antibodies, and the anti-body-virus complex is phagocytosed by macrophages. 

Early in the effort to develop a drug to treat HIV infection, researchers found that the virus had one potentially important "weak link in its life cycle. During the process of replication, the virus produces a very long polypeptide chain made of thousands of amino acids. This chain is similar to a protein except that it is much larger than a typical protein, so it is sometimes called a superprotein or a polyprotein. It is a polypeptide that contains within itself a number of individual proteins that the virus needs later in its replication. Some of those proteins are used to make the structural components of the cell, while others are used to make the cell s "working parts," nucleic acids and enzymes. 

The use of antibiotics for the control of plant virus diseases( ) is of interest. Several antibiotics have been tested for inhibition of replication of viral nucleic acid and/or protein synthesis within the host cell. Chloramphenicol, cycloheximide, actinomycin D and others are the most used antibiotics and the disease caused by tobacco mosaic... 

Possee, R. D. and Howard, S. C. (1987). Analysis of the polyhedrin gene promoter of the Autographa califor-nica nudear polyhedrosis virus. Nucleic Acids Res. 15, 10233-10248. 

The capacity of each step of the extraction and purification procedure to remove and/or inactivate contaminating substances derived from the host cell or culture medium, including, in particular, virus particles, proteins, nucleic acids and added substances, must be validated. 

Viruses are obligate intracellular parasites that use many of the host cell s biochemical mechanisms and products to sustain their viability. A mature virus (virion) can exist outside a host cell and still retain its infective properties. However, to reproduce, the virus must enter the host cell, take over the host cell s mechanisms for nucleic acid and protein synthesis, and direct the host cell to make new viral particles. 

Assembly of new virus particles from nucleic acids and proteins (from steps 4 and 5)... 

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