Synthesis viruses affecting

Jay, F. T., Laughlin, C. A. and Carter, B. J. (1981). Eukaryotic translational control Adeno-associated virus protein synthesis is affected by a mutation in the adenovirus DNA-binding protein. Proc. Natl. Acad. Sci. USA 78, 2927-2931. 

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... 

AZT works by specifically blocking DNA synthesis carried out by HIV reverse transcriptase. Other related compounds are also being tested to see if they specifically affect HIV reverse transcriptase. Such compounds might have equivalent antiviral effects. If they have fewer side effects than AZT, they may be even more effective in treating HIV-infected individuals. Two additional antivirals related to AZT have recently been approved for anti-HIV therapy, dideoxy-inosine (DDI) and dideoxycytosine (DDC). These drugs are predominantly recommended for individuals who cannot tolerate AZT, or for whom AZT has ceased to be effective although they are effective against HIV, they do have side effects. Nevertheless, they may be important because AZT does not indefinitely reduce the amount of virus in HIV-infected individuals. 

The majority of antiviral drugs which are under clinical development today generally interrupt viral nucleic acid synthesis. These compounds often do not affect host cell metabolism and possess considerable selectivity against virus-induced enzymes. This article discusses agents exhibiting significant antiviral activity against viral infections in animal model systems. 

Recently, lamivudine [LAM ih vue deen] or (-)-2 -deoxy-3 -thiacyti-dine (3TC) has been approved for treatment of HIV in combination with zidovudine. This dideoxynucleoside terminates the synthesis of the proviral DNA chain and also inhibits reverse-transcriptase of both HIV and hepatitis B virus (HBV). However, it does not affect mitochondrial DNA synthesis or bone marrow precursor cells. Resistance to zidovudine develops more slowly with the combination. Lamivudine has good bioavailability on oral administration and depends on the kidney for excretion. Though generally well tolerated, pancreatitis develops in a significant number of pediatric... 

The infectious elementary bodies of trachoma agent belong to the Chlamydiae which are parasites of mammalian cells and are considered unusually small bacterial cells. As in the case of vaccinia virus, only certain ansamycins, e.g. rifampicin at very high concentrations, affect the growth of trachoma agent. The mechanism of action is not known, but again RNA synthesis is not involved. 

Deletion Mutants - Another approach has been the construction of deletion mutants by the judicious use of restriction enz3mies and appropriate exonucleases. The sites of the deletions were mapped in some Instances they were widely separated but still affected a single protein. The functional ability of the mutants was then determined. The results, while at an early stage, are in agreement with the conclusions reached with the temperature-sensitive mutants. The early proteins must be functional to effect DNA replication, stimulation of host cell DNA synthesis and cell transformation. Interestingly, not all three of the late proteins appear to be required for virus production. Much more will surely come from these studies. 

Castanospermine has been screened for efficacy against simian immunodeficiency virus (265), and has been shown to prevent syncytium formation in feline astrocyte cultures infected with the feline immimodeficiency virus by modifying the viral cell envelope (266). It suppressed syncytium formation and hemolytic activity in baby hamster kidney cells infected with Newcastle disease virus however, synthesis and cell surface expression of the hemagglutinin-neuraminidase glycoprotein in the viral envelope were not affected, which strengthens the hypothesis that poor transport of the parent alkaloid across membrane barriers may limit its therapeutic use (267). Both 239 and its 6-0-butanoyl ester had comparable relative toxicities and antiviral effects on Rauscher murine leukemia virus (268), but the ester was more potent than the parent alkaloid in inhibiting replication of Moloney murine leukemia virus (258). The ester was also active against herpes simplex viruses types 1 and 2 (269,270). In the latter case, conclusive evidence was provided for intracellular hydrolysis to 239. 

Ara-T, with significant activity against HSV-1 and -2, and varicella zoster virus (but little against cytomegalovirus) is selectively phosphorylated by HSV-induced deoxypyrimi-dine kinase, but not by thymidine kinase from uninfected cells. Thus inhibition of DNA synthesis affects viral replication, but not the growth of normal cells, which explains the observed selective toxicity. 

---