The Replication of Viral DNA

The replication of viral DNA usually depends upon the genes of both the host organism and the virus. For example, ts mutations in the E. coli genes dnaB, D, E, F, and G lead to a loss in ability to support... 

Acyclovir Antiviral agent Inhibits the replication of viral DNA... 

The outcome of infection by SV40 depends on the organism infected. When simian cells are infected, the virus enters the cell and loses its protein coat. The viral DNA is expressed first as mRNAs and then as proteins. The large-T protein is the first one made (Figure 14.6), triggering the replication of viral DNA, followed by viral coat proteins. The virus takes over the cellular machinery for both replication of DNA and protein synthesis. New virus particles are assembled, and eventually the infected cell bursts, releasing the new virus particles to infect other cells. 

Methisazone does not interfere with the replication of viral DNA, the synthesis of viral mRNA, or the functioning of early viral mRNA. However, by disorganizing the formation of late proteins, it prevents assembly of complete, infectious virions (Prusoff, 1967). The antiviral spectrum of this drug is wide, in vitro. It inhibits multiplication of all pox-viruses, and other DNA viruses too (e.g. the adenoviruses and varicella), as well as several groups of RNA viruses (e.g. poliomyelitis, common cold, influenza A and B, and some arboviruses). However, in Man, no benefit can be demonstrated in these diseases at any dose that does not cause intense nausea and vomiting (Turner, Bauer and Nimmo-Smith, 1962). 

The synthesis of cellular DNA, however, requires concomitant protein synthesis. The rate of DNA chain growth begins to fall within minutes after adding cycloheximide (Planck and Mueller, 1977 Sti-mac et al., 1977), suggesting the existence of a small pool of essential protein with a high rate of turnover. It is possible, therefore, that the decline of cellular DNA synthesis after infection with herpesvirus is a consequence of the inhibition of protein synthesis (Kaplan, 1973a). The fact that viral DNA may be synthesized after the early suppression of protein synthesis implies that, unlike cellular DNA synthesis, the replication of viral DNA does not depend on ongoing protein synthesis. This was indeed observed in early work with HSV (Newton, 1964 Roizman and Roane, 1964), PRV (Kaplan, 1973 ) and adenovirus (Horwitz et al., 1973). 

Infection of animal cells with herpesviruses is commonly, though not invariably, followed by inhibition of the synthesis of cellular DNA, RNA, and protein, phenomena collectively and colloquially known as host shut-off. Host shut-off precedes most of the more obvious cytopathic effects which are characteristic of the late stages of a lytic infection and often precedes the replication of viral DNA. In the 20 years or so that have passed since the phenomena were first observed, little positive information has accumulated concerning the means by which the virus suppresses the synthesis of cellular macromolecules while directing the synthesis of its own. 

Methisazone does not interfere with the replication of viral DNA, the synthesis of viral mRNA, or the functioning of early viral mRNA. However, by disorganizing the formation of late proteins, it prevents assembly of complete, infectious virions (Woodson and Joklik, 1965 Prusoff, 1967). 

Li+ has significant inhibitory effects upon DNA viruses, in particular HSV which has been studied in depth. It was originally shown that Li+ inhibits viral replication in a dose-dependent, reversible manner in HSV-infected baby hamster kidney cells [240], and this has been found to be due to a Li+-induced decrease in the synthesis of viral DNA [241]. It is now well established that Li+ inhibits DNA synthesis in HSV types 1 and 2 and in several other DNA viruses, including measles, vaccinia, adenovirus, poxvirus, pseudorabies virus, Epstein-Barr virus, and the bovine, equine, and canine HV s [241]. Interestingly, Li+ has no effect on the replication of RNA viruses, such as influenza or encephalomyo-carditis virus. 

Mechanism of Action An antiviral that inhibits the enzyme DNA polymerase, causing DNA chain termination after its incorporation into viral DNA. Therapeutic Effect Prevents cell replication of 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... 

A multinuclear-activation galactosidase indicator (MAGI) infectivity assay was then used to determine the inhibitory stage of bevirimat. It was realised that bevirimat blocks virus replication at a time point after the completion of viral DNA integration and Tat expression.15 Furthermore, several assays, including quantitative radioimmunoprecipitation analysis, demonstrated that bevirimat does not affect virus particle release. 

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... 

Because herpesviruses express proteins that are not dependent on viral DNA synthesis, caution must be taken when determining the efficacy of a compound by IFA. Inhibition of virus replication would be more directly reflected by measuring the concentration of viral DNA (see Subheading 3.7.2.), However, the IFA is useful when compounds are being evaluated for use in kinetic studies of virus gene expression. Infected cultures will usually become IFA-positive 3 d post infection, reaching a peak of virus-infected cells at approx 7 d post infection. The method consists of two steps slide preparation and staining. 

Researchers have set out to target almost all stages in the life cycle of HIV, but the drugs currently available fall into two main types. The earliest developed were the reverse transcriptase inhibitors, e.g. AZT (Structure 4.2), which stop the replication of viral genes. Transcription is the process in which the DNA base sequence is... 

Standard experiments to determine the method by which schumannificine exerted its effect revealed that it prevented the infection of the host cell by the HIV by binding to the gpl20 on the viral coat. Some glycosidase inhibition was also noted which may contribute to the antiviral effect since this enzyme is important in the formation of new viral material after infection and replication of viral DNA in the host cell [43]. Schumannificine did not possess any reverse transcriptase or proteinase activity. 

Since the inhibition of viral DNA synthesis is dependent upon the amount of ACV-TP/GCV-TP formed in infected cells, the increase in intracellular ACV-TP/GCV-TP levels should facilitate the binding of ACV-TP/GCV-TP to HSV-1 DNA polymerase, and thereby promote the inhibition of virus replication. The mechanism of increase in ACV-TP/GCV-TP by SDC is not known. Stimulation of viral TK activity by SDC might be a possible mechanism. Effects of SDC on TK as well as expression of TK gene are under investigation. 

The transcriptional repression can be broken, however, leading to excision of the viral chromosome from the host genome as a circular DNA, followed by replication of viral DNA, followed by activation of genes needed to assemble virus particles. 

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