Epstein-Barr virus inhibition

Epstein-Barr virus (EBV) Burkitt s lymphoma, nasopharyngeal carcinoma, lymphoproliterative disorders in immuno-suppressed patients (e.g., AIDS, transplant recipients) EBNA-1 Inhibition of cell proliferation... 

Nasimuzzaman M, Kuroda M, Dohno S, Yamamoto T, Iwatsuki K, Matsuzaki S, Mohammad R, Kumita W, Mizuguchi H, Hayakawa T, Nakamura H, Taguchi T, Wakiguchi H, Imai S (2005) Eradication of Epstein-Barr virus episome and associated inhibition of infected tumor cell growth by adenovirus vector-mediated transduction of dominant-negative EBNAl. Mol Ther 11 578-590... 

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV) is clinically useful in the treatment of infections caused by several members of the herpes virus (e.g., herpes simplex, varicella zoster and Epstein-Barr virus [2,38,39]). An enzyme coded for by the virus phosphorylates ACV to a monophosphate intermediate. This species in turn undergoes further phosphorylation to a triphosphate with the aid of normal cell enzymes. Then, ACV triphosphate inhibits the herpes virus DNA... 

Inhibition and stimulation of LOX activity occurs as a rule by a free radical mechanism. Riendeau et al. [8] showed that hydroperoxide activation of 5-LOX is product-specific and can be stimulated by 5-HPETE and hydrogen peroxide. NADPH, FAD, Fe2+ ions, and Fe3+(EDTA) complex markedly increased the formation of oxidized products while NADH and 5-HETE were inhibitory. Jones et al. [9] also demonstrated that another hydroperoxide 13(5)-hydroperoxy-9,ll( , Z)-octadecadienoic acid (13-HPOD) (formed by the oxidation of linoleic acid by soybean LOX) activated the inactive ferrous form of the enzyme. These authors suggested that 13-HPOD attached to LOX and affected its activation through the formation of a protein radical. Werz et al. [10] showed that reactive oxygen species produced by xanthine oxidase, granulocytes, or mitochondria activated 5-LOX in the Epstein Barr virus-transformed B-lymphocytes. 

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. 

Dhar SK, Yoshida K, Machida Y, Khaira P, Chaudhuri B, Wohlschlegel JA, Leffak M, Yates J, Dutta A (2001) Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Cell 106 287-296. 

Dantuma NP, Heessen S, Lindsten K, Jellne M, and Masucci MG (2000a) Inhibition of proteasomal degradation by the Gly-Ala repeat of Epstein-Barr virus is influenced by the length of the repeat and the strength of the degradation signal. Proc. Natl. Acad. Sci. U.S.A. 97 8381-8385. 

Levitskaya J, Coram m, Levitsky V, Imreh S, Stegerwald-Mullen PM, Klein G, Kurilla MG, and Masucci MG (1995) Inhibition of antigen processing by the internal repeat region of the Epstein-Barr Virus nuclear antigen-1. Nature (London) 375 685-688. 

Pharmacology Ganciclovir, a synthetic guanine derivative active against CMV, is an acyclic nucleoside analog of 2 -deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Sensitive human viruses include CMV, herpes simplex virus (HSV)-I and -2, herpes virus type 6, Epstein-Barr virus, varicella-zoster virus, and hepatitis B virus. 

Epstein-Barr virus early antigen induction. Methanol extract of the dried leaf, in cell culture at a concentration of 1 pg/mL, was inactive. The assay was designed for tumor-promoting activity . Two diastere-oisomers of 2,7,1 l-cembratriene-4,6-diol (a- and 3-CBT) from the neutral fractions of cigarette smoke condensate, in Raji cells, produced potent inhibitory effects on the induction of Epstein-Barr virus (EBV)-EA by 12-0-tetradecanoylphorbol-13-acetate (TPA). The doses of a- and P-CBT required for 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7 mg/mL, respectively. Application of a- and P-CBT to mouse skin before treatment with TPA, inhibited TPA-induced ornithine decarboxylase activity in a dose-dependent manner. Application of 16.5 pM/mouse of a- and p-CBT resulted... 

Okada, N., K. Takebayashi, ]. Kawa-shima, et al. Inhibition of Epstein-Barr virus (EBV) activation by triterpenes in Sesamum indicum L. callus. Shoku- S1084 butsu Soshiki Baiyo 1994 11(2) ... 

It is an acyclic guanosine analog which require triphosphorylation for activation prior to inhibition of viral DNA polymerase. It is active against cytomegalovirus (CMV), varicellazoster virus, Epstein-Barr virus and human herpes virus-8. It is almost 100 times more potent than acyclovir against CMV. 

CMP, CDP, CTP, and synthetic derivatives of these nueleotides have been found to inhibit sialyltransferase activity.301" 02 Interest in such inhibitors is increasing, as they may be expected to serve as anticancer agents.269 901,303 Therefore, regulation of Golgi sialyltransferase activity appears possible by nucleotides as products of sialyl- and other glycosyl-transferase activities.1" 2 Interestingly, Epstein-Barr virus infection of human B, lymphoblastoid cell-lines leads to a diminution of sialyltransferase activity.304... 

EBV Inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA [22-27]... 

In contrast to antibacterial antibiotic therapy, inhibition of viral replication is usually difficult to achieve. Therefore preventive strategies, such as vaccination, are frequendy more successful and clinically important. However, vaccines are not available for all viruses furthermore, some viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), are ubiquitously present and usually not very pathogenic unless in an immunocompromised host. One strategy to combat viral infecdons in the immunocompromised host is the application of neutralizing mAbs. One such mAh is directed to the F protein of the respiratory syncytial virus (RSV), which afflicts premature newborns with often severe pulmonary infections this mAh appears to be useful in such situations (91). Other mAbs to viral antigens are in development. 

Salek-Ardakani S, Arrand JR, Mackett M. Epstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7 expression on human monocytes implications for immune evasion by EBV. Virology 2002 304 342-51. 

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