Studies on mammalian viral DNA and its metabolism, with special reference to herpes virus

Morrison, James M (1968) Studies on mammalian viral DNA and its metabolism, with special reference to herpes virus. PhD thesis, University of Glasgow.

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The information content of the DNA of herpes virus, and its expression in the infected cell, have been studied by two main approaches. The first approach has been the study of two enzymes, alkaline deoxyribonuclease (DNase) and DNA polymerase, which are found in markedly increased levels in herpes-infected cells. It has been shown that the induction of these enzymes after infection required synthesis of mRNA and protein, and that the induced enzymes differ from those found in the non-infected cell in several of their enzymic properties. Partial purification of the induced enzymes has been undertaken and, in the case of the herpes-induced DNase, separation from the corresponding host cell enzyme activity has been achieved. The induced DNase is a DNA-specific exonuclease attacking both native and denatured DNA, and releasing 5'-monophosphates, probably from the 3'-hydroxyl terminus. It has been shown that pseudorabies virus induces a similar enzyme. The alkaline DNase of the host cell is an endonuclease, preferentially attacking denatured DNA. Immunological methods have been used to determine the specificities of the induced enzymes. Serum from rabbits immunised against high-speed supernatant fractions of herpes-infected rabbit kidney cells inhibits the DNase and DNA polymerase induced by herpes virus in BHK 21 and HEp-2 cells, but not the corresponding enzymes of non-infected or pseudorabies-infected cells. The significance of these results and of experiments on the synthesis of cellular and viral DNA is discussed in terms of two problems:- (i) Does the information for the amino acid sequence of the induced enzymes reside in the nucleotide sequence of the genome of the host cell or of the invading virus? (ii) What roles do the induced enzymes play in the infective process? The results obtained suggest that the, enzymes are virus-specified. The possible roles of the induced enzymes are discussed in the light of this and other evidence. The second approach, has been to examine possible - difficulties in translation encountered by the virus when using the protein-synthetic mechanisms of the host cell. One of the few methods of obtaining information on the primary structure of DNA molecules is the technique of nearest neighbour frequency analysis. Analyses of nine animal DNA viruses have been performed and the patterns obtained compared with that of the mammalian host. The most outstanding feature of the nearest neighbour pattern of the DNA of mammalian cells is the marked rarity of the dinucleotide CpG. The viruses examined were broadly divisible into two groups; one, comprising members of the papovavirus group, which closely resembled the host cell pattern, especially in the rarity of CpG, and the other - comprising three viruses of the herpes group and one member each of the adenovirus and poxvirus groups - had patterns which deviated much less from random expectation. If the assumption is made that the greater part of DNA specifies polypeptides, then the nearest neighbour pattern of the DNA will reflect the frequency of occurrence of the various dinucleotides in the codons being used for protein synthesis. Thus, in the mammalian cell, CpG-containing codons must be infrequently used, if at all, while, during virus-specific protein synthesis in cells infected with, for example, herpes virus, such codons will frequently require translation. If one now makes a second assumption, namely that, in a given cell, the transfer RNA population is optimally adapted to the translation of the genome of that cell, then entry into that cell of a virus such as herpes whose DNA contains certain codons rarely, if ever, found in the non-infected cell will present the virus with a situation in which the existing tRNA population is not optimally adapted to the translation requirements of the viral genome. Granted, the above rationale, the synthesis of virus-specified tRNAs in the infected cell is a reasonable proposition. Evidence for the occurrence of a new arginyl-tRNA in herpes-infected cells has been obtained by other workers. Four of the six oodons for the arginine are the CpG-containing triplets OGA, CGC, GCG and OGU.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: H M Keir
Keywords: Biochemistry, Virology
Date of Award: 1968
Depositing User: Enlighten Team
Unique ID: glathesis:1968-72356
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 24 May 2019 15:12
Last Modified: 24 May 2019 15:12

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