DNA replication viral

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... 

Aciclovir is phosphorylated preferentially by herpes simplex virus-coded thymidine kinase and following further phosphorylation aciclovir triphosphate interferes with herpes virus DNA polymerase and viral DNA replication. Aciclovir topical cream is indicated in the management of initial genital herpes and in limited non-life threatening mucocutaneous herpes simplex virus infections in immunocompromised patients. 

Acyclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA. 

Mechanism of Action. Acyclovir inhibits viral DNA replication by inhibiting the function of the DNA polymerase enzyme.42 This drug is taken into virus-infected cells and converted to acyclovir triphosphate by an enzyme known as viral thymidine kinase 42 The phosphorylated drug directly inhibits the function of the viral DNA polymerase, thus impairing the replication of viral genetic material. The virus also incorporates the drug into viral DNA strands, which halts further production of DNA because of the presence of a false nucleic acid.42... 

Mechanism of Action. Cidofovir works like acyclovir and ganciclovir these drugs inhibit viral DNA replication by inhibiting DNA polymerase activity and by halting elongation of viral DNA chains.42... 

Mechanism of Action. Foscarnet works somewhat like acyclovir and ganciclovir that is, foscarnet inhibits the DNA polymerase enzyme necessary for viral DNA replication. Foscarnet differs from these other antiviral drugs, however, in that it does not require phosphorylation (activation) by enzymes such as viral thymidine kinase. Certain strains of viruses are thymidine-kinase deficient, meaning that these viruses lack the enzyme needed to activate antiviral agents... 

Mechanism of Action. Vidarabine appears to exert its antiviral effects in a manner similar to acyclovir (see section on Acyclovir ). Both drugs selectively inhibit viral enzymes that are responsible for viral DNA replication.42... 

Chejanovsky, N. and Carter, B. J. (1989). Mutagenesis of an AUG codon in the adeno-associated virus rep gene Effects on viral DNA replication. Virology 173, 120-128. 

Bacteriophage lambda (X) is a good example for considering phage infection. In lytic infection, the injected linear double-stranded X DNA first circularizes. It is then transcribed to produce viral proteins needed for viral DNA replication and packaging as well as many molecules of viral capsid proteins. The viral DNA is replicated and the DNA copies are packaged into new phage... 

The genetically complex AcAfNPV prototype baculovirus genome is a double-stranded, covalently closed circular molecule with superhelical conformation and a size of approximately 130 kbp (12). Regulation of viral gene expression is temporally organized relative to the time of viral DNA replication which occurs at approximately 6 hours post infection in cultured insect cells. By our functional criteria, some of the early genes (Table I) are described as immediate early because they are expressed immediately in a viral infection or transient expression assay, or do not require... 

Inhibition of viral mRNA function Inhibition of viral DNA replication via the inhibition of specific polymerases Inhibition of low molecularweight polypeptide gene products... 

Inhibition of viral DNA replication using nucleoside analogues (e.g. idoxuridine against herpesvirus)... 

The antiviral nucleosides aciclovir and ganciclovir are also converted to their respective nucleoside triphosphates in the cytoplasm of infected cells. They proceed to inhibit viral DNA replication either by inhibition of the DNA polymerase or by incorporation into DNA with subsequent termination of chain extension. Finally the anti-HIV drug AZT acts in an analogous manner, being converted to the corresponding triphosphate and inhibiting viral RNA synthesis by the HIV reverse transcriptase. 

Temperature-sensitive Mutants - A number of temperature-sensitive mutants of SV40 have been analyzed. Those found defective in the complementation A group and the physical map regions which code for the early proteins (T antigen and t) were also found defective in their ability to transform cells. The temperature-sensitive transformation defect was reversible at permissive temperatures, i.e., transformed colonies appeared. Mutants defective in the formation of late proteins (viral structural proteins) were able to transform cells. Therefore, functional early proteins are required to effect and maintain transformation. The early proteins necessary for transformation also permit viral DNA replication and the stimulation of host cell DNA synthesis. The exact biochemical functions required for transformation have not yet been determined. 

Famciclovir is an antiherpes virus agent that converts to penciclovir, which inhibits viral DNA replication by interfering with viral DNA polymerase. It is indicated in the treatment of acute herpes zoster treatment or suppression of recurrent genital herpes in immunocompetent patients and treatment of recurrent mucocutaneous herpes simplex infections in HIV-infected patients. 

This drug is deaminated intracellularly and phosphorylated. The phosphorylated form (Ara-A) is similar to adenosine triphosphate (ATP), and, when incorporated into the viral DNA replication sequence, binds to DNA polymerase and inhibits DNA synthesis. 

FIGURE 49 2 Conversion of acyclovir to acyclovir triphosphate leading to DNA chain termination. Acyclovir is converted to the monophosphate (MP) derivative by a herpes virus thymidine kinase. Acyclovir-MP is dien phosphory-lated to acyclovir-DP and acyclovir-TP by cellular enzymes. Uninfected cells convert very little or no drug to the phos-phorylated derivatives. Thus, acyclovir is selectively activated in cells infected with herpesviruses that code for appropriate thymidine kinases. Incorporation of acyclovir-MP from acyclovir-TP into the primer strand during viral DNA replication leads to chain termination and formation of an inactive complex with the viral DNA polymerase. (Adapted from Elion, 1982, with permission.)... 

When a virus infects a cell, it could induce its host to make deoxyribonucleotides for viral DNA replication by means of the cellular enzyme (probably derepressed after infection), or the virus could carry its own specific ribonucleotide reductase genes which are expressed in the host cell and produce a new enzyme. Ribonucleotide reductase of herpes simplex virus is even considered the transforming function of However virus-... 

---