Herpes virus infection

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of "antiviral proteins." These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-P), or lymphocytes (IFN-y). Interferons are also used to treat certain malignancies and autoimmune disorders (e.g., IFN-a for chronic hepatitis C and hairy cell leukemia IFN-p for severe herpes virus infections and multiple sclerosis). 

Many chemicals (including pharmaceuticals but also environmental and occupational chemicals) are known to stimulate the immune system in a way that autoimmune diseases occur [61]. However, because of its multifactorial nature, the occurrence of autoimmune-like (including drug allergic) diseases is rare if considered on a compound-by-compound base. But, in some cases (e.g., in case of HIV or Herpes virus-infected individuals), adverse reactions occur at a higher rate [65, 66]. 

Antiviral activity. Water extract of the dried fruit, in cell culture at a concentration of 10%, was inactive on herpes virus-type 2, influenza, poliovirus, and vaccina . Tincture of the dried fruit, administered orally to adults of both sexes at a dose of 60 mL/person, was active on herpes virus. PCT patent number W096/14064 reported treatment of six subjects with herpes virus infections. The activity was highly dose... 

Levamisole (6-phenyl-2,3,5.6-lelraliydroimidazol[2,1 -hjdiiazole), C11H12N2S (3), was found to be effective against herpes virus infections in humans. 

Aphidicolin has been used to treat herpes virus infections of the eye. Its structure is ... 

Famciclovir is rapidly converted to penciclovir in intestinal and liver tissue after oral administration. More than half of an oral dose of famciclovir is excreted in the urine as unchanged penciclovir. The plasma elimination half-life of penciclovir is about 2h, similar to that of acyclovir however, the intracellular half-life of penciclovir in herpes virus-infected cells is considerably longer than that of acyclovir. 

In histomorphological terms, hepatitis means inflammation of the liver . The factor causing the disease may spread from the initially or predominantly affected mesenchyma to the liver cells (such as in kala-azar and malaria), or the primarily or mainly affected Hver cells may subsequently incorporate the mesen-ch)mia into the damaging process (as for example in yellow fever). In leptospirosis and herpes virus infection, the morphological finding is determined almost exclusively by changes in the parenchyma, while mesench)mial reactions are hardly or not at all present. 

Abnormal hair growth (54), herpes virus infections (55), and malignant changes in smallpox vaccination scars have also been observed (56,57). Allergic skin reactions sometimes occur, for example urticaria and purpura (58) and possibly photosensitivity reactions. 

Selby PJ, Powles RE, Jameson B, Kay HEM, Watson JG, Thornton R, Morgenstern G, Clink HM. Parenteral acyclovir therapy for herpes virus infections Inman. Lancet 1979 2 1267-1270. 

Amino-9-a-D-arabinofuranosyl-8-azapurine showed strong antiviral action in vitro against seven virus species. However, it proved ineffective against lethal herpes virus infections in mice and against several other... 

This chapter is a review of the antimicrobial susceptibilities of the causative organisms and the treatment of the sexually transmitted infections most prevalent in North America and Western Europe, gonorrhea, nongonococcal urethritis, genital herpes virus infections, and trichomoniasis. Because of their relative rarity or because no important advances in therapy have been made in the past decade, syphilis, lymphogranuloma venereum, chancroid, and granuloma inguinale are not considered. 

Amino-5-iodo-2, 5 -dideoxyuridine [56045-73-9] (13) C9H12IN304, was synthesized in 1975 (27) and was found effective against herpes keratitis in rabbits (28). This compound is markedly less cytotoxic than IdU, indicating 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 viruses. The specific antiviral activity of (13) is considered to be a result of the incorporation of the 5 -IV-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 virus-infected cells, brought about by a virus-induced thymidine kinase (29). 

Trifluridine, C10H11F3N2O5, (5-trifluoromethyl-2,-deoxyuridine [70-00-8], F3TdU, 14) was first prepared (30) in 1962. It is used for topical therapy of herpes virus-infected eyes. It is especially useful for treating infections that are resistant to IdU therapy. Like IdU, trifluridine is incorporated into DNA in place of thymidine in both infected and uninfected cells. But it is 10 times more potent than IdU against herpes keratitis in rabbits and 10 times more soluble in water. Trifluridine is also useful in treating human cytomegalovirus (HCMV), but its toxicity to bone marrow may limit its clinical use. 

The antiviral mechanism of action of acyclovir has been reviewed (72). Acyclovir is converted to the monophosphate in herpes virus-infected cells (but only to a limited extent in uninfected cells) by viral-induced thymidine kinase. It is then further phosphorylated by host cell guanosine monophosphate (GMP) kinase to acyclovir diphosphate [66341-17-1]y which in turn is phosphorylated to the triphosphate by unidentified cellular enzymes. Acyclovir triphosphate [66341 -18-2] inhibits HSV-1 viral DNA polymerase but not cellular DNA polymerase. As a result, acyclovir is 300 to 3000 times more toxic to herpes viruses in an HSV-infected cell than to the cell itself. Studies have shown that a once-daily dose of acyclovir is effective in prevention of recurrent HSV-2 genital herpes (1). HCMV, on the other hand, is relatively uninhibited by acyclovir. 

Acyclovir was the first antiherpetic agent to selectively inhibit herpes virus replication while maintaining an excellent safety profile, and currently constitutes the standard therapy for the management of herpes virus infections. 

Dose. For herpes virus infections in immunosupressedpatients up to 10 mg per kg body-weight every 8 hours. 

Dose. For viral hepatitis, influenza and herpes virus infections upto 1 g per day in divided... 

Perry CM, Faulds D. Valaciclovir, a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpes virus infection. Drugs 1996 52 754-772. 

The interferon-inducing ability of poly I C was first demonstrated in cell systems in 1968 [105] and this was shortly followed by details of its curative effects on a herpes virus infection of a rabbit s eye [106], and on various virus infections of animals [107]. Since then there have been a large numbo- of papers on its antiviral activity in vitro and in vivo. Human cell cultures appear to be protected against the common respiratory viruses at doses of poly I C (01-10 pg/ml) which are much lower than those required to induce detectable interferon (50 pg/ml) [108]. This and similar observations pose difficult questions as to the mode of action of poly I C. It has been suggested that small doses of the compound result in the synthesis of a pre-interferon which can produce an antiviral state without detectable free interferon. This pre-interferon can be converted to detectable interferon by antimetabolites, endotoxin or by larger doses of poly I C itself [109]. 

Its principal use is against superficial herpes virus infections of humans in which it produces a moderate cure rate without harming the tissue to which the drug is applied. Since dermal herpes simplex is usually self-limiting and of short duration, the assessment of clinical effect is not easy when double-blind trials are carried out. Some authors claim that a statistically positive result is obtained and an almost equal number conclude that the difference between drug and placebo treated patients is not significant. Some patients, however, consider the treatment to be beneficial [190]. 

Zisman B, Hirsch MS, Allison AC. Selective effects of anti-macrophage serum, silica and anti-lymphocyte serum on pathogenesis of herpes virus infection of young adult mice. J Immunol... 

Huard B, Friih K (2000) A role for MHC class I down-regulation in NK cell lysis of herpes virus-infected cells. Eur J Immunol 30 509-515... 

Borysiewicz LK, Sissons JG (1994) Cytotoxic T cells and human herpes virus infections. Curr Top Microbiol Immunol 189 123-150... 

Previous studies demonstrated the antiviral activity of ascorbate against a broad spectrum of RNA and DNA viruses in vitro (1-4) and in vivo (5, 6). It has been claimed that ascorbate inhibited the activation of a latent human retrovirus (human T-cell leukemia virus 1) induced by 5-iodo-2 -deoxyuridine and JV-methyl-A/ -nitro-A-nitrosoguanidine (7). However, it was not established whether ascorbate exerted a virus-specific effect or interacted directly with the activating substances. In addition, the effects of ascorbate on acute infection by human retroviruses have not been determined. In vivo, oral, and intravenous administration of ascorbate is said to have produced clinical improvements in patients afflicted with influenza, hepatitis, and herpes virus infections, including infectious mononucleosis (5, 6). Clinical improvement was claimed in AIDS patients who voluntarily ingested high doses of ascorbic acid (8). 

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