DNA, animal virus

In a variety of tissue culture systems, 3-DZA exerts a powerful antiviral action against broad range of RNA and DNA animal viruses. With J. Bader, we have studied in some detail the antiviral activity of 3-DZA on Rous sarcoma virus (RSV) infection in chick embryo fibroblasts ... 

Many animal viruses, particularly the oncogenic viruses—either directly or, in the case of RNA viruses such as HIV that causes AIDS, their DNA transcripts generated by the action of the viral RNA-dependent... 

The multiple sites that serve as origins for DNA replication in eukaryotes are poorly defined except in a few animal viruses and in yeast. However, it is clear that initiation is regulated both spatially and temporaUy, since clusters of adjacent sites initiate rephcation synchronously. There are suggestions that functional domains of chromatin replicate as intact units, implying that the origins of rephcation are specificaUy located with respect to transcription units. 

We have discussed in a general way the nature of animal viruses in the first part of this chapter. Now we discuss in some detail the structure and molecular biology of a number of important animal viruses. Viruses will be discussed which illustrate different ways of replicating, and both RNA and DNA viruses will be covered. One group of animal viruses, those called the retroviruses, have both an RNA and a DNA phase of replication. Retroviruses are especially interesting not only because of their unusual mode of replication, but because retroviruses cause such important diseases as certain cancers and acquired immunodeficiency syndrome (AIDS). 

Classification of animal viruses Most of the animal viruses which have been studied in any detail have been those which have been amenable to cultivation in cell cultures. As seen, animal viruses are known with either single-stranded or doublestranded DNA or RNA. Some animal viruses are enveloped, others are naked. Size varies greatly, from those large enough to be just visible in the light microscope, to those so tiny that they are hard to see well even in the electron microscope. In the following sections, we will discuss characteristics and manner of multiplication of some of the most important and best-studied animal viruses. 

Each type of virus has different attributes, so several classes of animal viruses are being engineered as vectors to transform mammalian cells. Adenoviruses, for example, lack a mechanism for integrating DNA into a chromosome. Recombinant DNA introduced via an adenoviral vector is therefore expressed for only a short time and then destroyed. This can be useful if the objective is transient expression of a gene. 

A vector is a molecule of DNA to which the fragment of DNA to be cloned is joined. Essential properties of a vector include 1) it must be capable of autonomous replication within a host cell, 2) it must contain at least one specific nucleotide sequence recognized by a restriction endonuclease, and 3) it must carry at least one gene that confers the ability to select for the vector, such as an antibiotic resistance gene. Commonly used vectors include plasmids and bacterial and animal viruses. 

Transferring genes with engineered animal viruses. There is special interest in transferring cloned DNA into human cells to correct genetic defects.155 Transfer of human genes into other animals is also important for a variety of reasons. For example, human proteins of therapeutic value could be produced in animal milk. Animals can be engineered to have defects that mimic those in humans and which can then be studied in animals.156... 

Electrophoretic patterns of highly supercoiled or partially supercoiled DNA. Strip A represents a sample of circular duplex DNA obtained by deproteinization of the animal virus SV40. In strips B and C the DNA has been exposed for increasing times to an enzyme (topoisomerase) that catalyzes relaxation. Adjacent bands differ by 1 in linking number. (From W. Keller, Characterization of purified DNA-relaxing enzyme from human tissue culture cells, Proc. Natl. Acad. Sci. USA 72 2553, 1975.)... 

Hepatitis B is an animal virus with a small circular DNA genome. A gap in one strand is bridged by an incomplete complementary strand. The longer strand has a protein bound at its 5 end. A DNA polymerase present in the mature virus particle can elongate the 3 ends of the incomplete strands. An unusual feature of this virus is that replication involves an RNA intermediate that must be reverse transcribed. 

Enzymes that catalyze the synthesis of DNA using an RNA template are known as reverse transcriptases. The first reverse transcriptase discovered was encoded by an RNA retrovirus. This enzyme is needed in the virus replication cycle. Some animal viruses pass through an RNA intermediate and also require a reverse transcriptase to replicate the viral DNA. Similarly, a number of transposable elements found in cellular chromosomes replicate through RNA intermediates they usually encode a reverse transcriptase. A unique reverse transcriptase called telomerase is used to synthesize the DNA at the ends of linear eukaryotic chromosomes. 

The rDNA-derived products may contain potentially harmful contaminants that are normally not present in their equivalents prepared by chemical methods, and which the purification process must be capable of eliminating, such as the endotoxins expressed in bacterial cells, cellular DNA, and viruses of animal origin. Contamination with nucleic acid from transformed mammalian cells is of particular concern due to the possible presence of potentially oncogenic DNA. 

A common feature of many animal viruses is their capacity to induce programmed cell death (apoptosis), a process characterized by cell shrinkage, nuclear condensation, and DNA fragmentation (Shen and Shenk, 1995). Apoptosis may serve as a host defense to limit virus growth, or it may promote virus spread or enhance viral replication via activation of one or more signaling pathways involved in apoptosis induction (Teodoro and Branton, 1997). 

Molecular biology also involves organic chemistry, physics, and biophysical chemistry as it deals with the physicochemical structure of macromolecules (nucleic acids, proteins, lipids, and carbohydrates) and their interactions. Genetic materials including DNA in most of the living forms or RNA (ribonucleic acid) in all plant viruses and in some animal viruses remain the subjects of intense study. 

Transplacental transfer of asbestos may occur, but this has not been linked with any adverse reproductive outcomes in humans. Results of animal studies do not indicate that exposure to asbestos is likely to result in birth defects. A recent study of brake workers, who are typically exposed to short chrysotile fibers, indicates that brake work does not increase the risk of mesothelioma. The results add to the evidence that fiber type and size are important determinants of mesothelioma risk. Along with asbestos, Simian virus 40 (SV40), a DNA monkey virus, has recently been implicated in the etiology of mesothelioma. It was proposed that SV40 and asbestos are possibly cocarcinogens. 

Other oncogenes were soon discovered in a variety of animal viruses, and as the techniques of DNA sequencing became more routine, a surprising number of these oncogenes were matched up with normal genes in animals and even in humans. But what was the role of these proto-oncogenes Most of them have now been shown to code for enzymes that help control the growth and differentiation of cells. In many instances, the enzymes are kinases that phosphorylate serine, threonine or tyrosine residues of other... 

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