Pseudorabies virus inhibition

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. 

Primary screening for antiviral activity was carried out using the agar-diffusion plaque-inhibition method with cylinders [65]. The compounds were tested against one representative in each of the four taxonomic viral groups namely, picoma-, orthomyxo-, paramyxo- and herpes viruses, which represent a few of the most important families of the human patogens. The viruses used were poliovirus 1 (PV1), influenza virus A (FPV), Newcastle disease virus (NDV) and pseudorabies virus (PsRV). 

Actinomycin D is a peptide antibiotic, produced by Streptomyces parvulu. It interacts with cellular DNA and inhibits the replication of mammalian viruses that depend on cellular functions, e.g., rabies virus [18]. Mithramycin is a related compound that inhibits influenza and pseudorabies viruses probably due to inhibition of host cell RNA polymerase II [18]. 

Schmidt, Schwarz and colleagues (47,48) further showed that 2F-mannose and 2F-glucose inhibited the biosyntheses of infective Semliki virus and fowl plague virus (influenza virus A) in chick embryo cells eind that of pseudorabies virus in rabbit kidney cells. This was attributed to failure to complete the viral envelope (49)... 

Ambagala AP, Hinkley S, Srikumaran S (2000) An early pseudorabies virus protein down-regulates porcine MHC class I expression by inhibition of transporter associated with antigen processing (TAP). J Immunol 164 93-99... 

Ben-Porat, T., and Kaplan, A. S., 1965, Mechanism of inhibition of cellular DNA synthesis by pseudorabies virus. Virology 25 22. 

Dubovi, E. J., and Youngner, J. S., 1976a, Inhibition of pseudorabies virus replication by vesicular stomatitis virus. I. Activity of infectious and inactivated B particles, J. Virol. 18 526. 

Pseudorabies virus apparently causes delayed, but not early, virion-associated shut-off. The inhibition of cellular protein synthesis by PRY is prevented by actinomycin (Ben-Porat et ah, 1971 Ihara et al., 1984). By labeling proteins during the hour immediately following reversal of a cycloheximide block it was shown that host pro-... 

Significant antiviral ejfectivity was shown in vitro for titanocene dichloride (I) against numerous DNA and RNA viruses in the extracellular phase Typical examples of viruses, which were inhibited by direct contact with I and lost infectivity up to 100%, were orthopoxvirus (vaccinia) and herpes virus (pseudorabies) as DNA viruses, and rhabdovirus (vesicular stomatitis), paramyxovirus (Newcastle disease) and diverse orthomyxoviruses (e.g. influenza A and B) as RNA viruses. A comparable antiviral effect against herpes viruses was detectable after application of the ferricenium salt whereas, on the other hand, vanadocene dichloride (11) and molybdenocene dichloride (V) failed to show antiviral activity under the same experimental conditions. 

Preliminary studies with azauridine suggest that this material was effective for the treatment of herpes simplex and zoster infections of the human eye (69). Rabbits infected with vaccinia virus vaccine were com-pletely protected from pustule formation and erythema by 2-3 grams of compound injected IV (70). This material apparently has a low order of toxicity. 5-Bromo-2-deoxyuridine was found to inhibit a new virus, equine herpes 3, in rabbit kidney cells as well as pseudorabies, a DMA. virus, whereas vesicular stomatitis, an RNA virus, was resistant (71). A large number of nucleosides have been synthesized and tested in various systems for antiviral activity. 1-p-D-Arabinofuranosylcytosine (cytarabine ara-C) blocked DNA synthesis of herpes-infected cells (72) while a number of structurally related compounds showed some antiviral activity, although less than the parent compound (73,74,75,76). It is still too early to determine the ultimate value of these newer agents as "antiviral" drugs. 

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