DNA, host

Amino-5-iodo-2, 5 -dideoxyuridine [56045-73-9] (13) C2H22IN2O4, was synthesized ia 1975 (27) and was found effective against herpes keratitis ia rabbits (28). This compound is markedly less cytotoxic than IdU, iadicating that it may have a safer and more specific mode of antiviral activity. A potential limitation of this group of nucleosides is their specificity, for they fail to inhibit all strains of herpes vimses. The specific antiviral activity of (13) is considered to be a result of the incorporation of the 5 -Ai-phosphate into both viral and host DNA in infected cells, but not into the DNA of normal cells. Phosphorylation of (13) occurs only in herpes vims-infected cells, brought about by a vims-induced thymidine kinase (29). 

After cleavage of the host DNA, both viral 3 -hydroxyl DNA ends are ligated to opposite strands of the acceptor DNA in a trans-esteritication reaction. Finally, for ligation to the acceptor DNA, the last two nucleotides at the 5 -end of the viral cDNA are trimmed and gap tilling is performed, probably carried out by host cell repair (Pommier et al. 2005). 

Plasmid A small, extrachromosomal, circular molecule of DNA that rephcates independendy of the host DNA. 

DNA at the sites where the restriction enzymes will act. Modification of host DNA is brought about by methylation of purine or pyrimidine bases. 

Figure 5.21 Consequences of infection by a temperate bacteriophage. The alternatives upon infection are integration of the virus DNA into the host DNA (lysogenization) or replication and release of mature virus (lysis). The lysogenic cell can also be induced to produce mature virus and lyse.

Figure 5.26 Integration of lambda DNA into the host. Integration always occurs at a specific site on the host DNA, involving a specific attachment site (att) on the phage. Some of the host genes near the attachment site are given. A sitespecific enzyme (integrase) is involved, and specific pairing of the complementary ends results in integration of phage DNA.

Figure 5.27 Bacteriophage Mu. (a) Genetic map of Mu. (Confusingly, there are two G s, the G gene and the invertible G segment. These are different G s.) (b) Integration of Mu into the host DNA, showing the generation of a five-base-pair duplication of host DNA.

Given the role of H. pylori infection in gastric cancer and duodenal ulcer disease, one must note that certain interleukin-1 gene cluster polymorphisms (suspected of increasing production of interleukin-1-/1) are associated with a predisposition to hypochlorhydria and gastric cancer [52]. One of these host DNA polymorphisms involves a TATA box. 

Vector used to introduce cloned gene into host DNA/nuclei... 

The life history of a retroviras is described in chapter 17 (see Figure 17.45). A summary is presented here. The genome of a retrovirus is composed of RNA not DNA but, when a retrovirus infects a host cell its RNA is transcribed into DNA, catalysed by the enzyme, reverse transcriptase. This DNA is then incorporated into the genome of the host. On transcription of the host DNA, during cell division, viral mRNA and viral genomic RNA are produced. The... 

Vidarabine s specific mechanism of action is not fully understood. Cellular enzymes convert this drug to a triphosphate that inhibits DNA polymerase activity. Vidarabine triphosphate competes with deoxyadeno-sine triphosphate (dATP) for access to DNA polymerase and also acts as a chain terminator. Although vidarabine is incorporated into host DNA to some extent, viral DNA polymerase is much more susceptible to inhibition by vidarabine. Vidarabine also inhibits ri-bonucleoside reductase and other enzymes. Resistance occurs as a result of DNA polymerase mutation. 

Trifluridine (trifluorothymidine) is a fluorinated pyrimidine nucleoside that inhibits viral DNA synthesis in HSV-1, HSV-2, CMV, vaccinia, and some adenoviruses. It is phosphorylated intracellularly by host cell enzymes, and then competes with thymidine triphosphate for incorporation by the viral DNA polymerase (Figure 49-3). Incorporation of trifluridine triphosphate into both viral and host DNA prevents its systemic use. Application of a 1% solution is effective in treating keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 or HSV-2. Cutaneous application of trifluridine solution, alone or in combination with interferon alfo, has been used successfully in the treatment of acyclovir-resistant HSV infections. 

The retroviral genomic RNA serves as the template for synthesis of a double-stranded DNA copy, the provirus (Figure 49-4). Synthesis of the provirus is mediated by a virus-encoded RNA-dependent DNA polymerase, or reverse transcriptase. The provirus is translocated to the nucleus and is integrated into host DNA. Transcription of this... 

Integration into host DNA All viral genes removed Relatively safe... 

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