Ben Nathan, D.; G. Maestroni; S. Lustig; A. Conti. Protective effects of melatonin in mice infected with encephalitis viruses. Archives of Virology. 1995. v. 140 (2) p. 223-230. ISSN: 0304-8608.

NAL Call No.:  448.3 Ar23

Descriptors: Semliki Forest virus, West Nile virus, melatonin, disease resistance, stress, mice, spleen, thymus gland, body weight, mortality, fatal infections, experimental infections.

Abstract: We examined the effect of the pineal neurohormone melatonin (MLT) on protection from viral encephalitis. The antiviral activity of MLT was evaluated in normal mice inoculated with Semliki Forest virus (SFV) and in stressed mice injected with the attenuated non-invasive West Nile virus (WN-25). Administration of MLT (s.c.) daily from 3 days before through 10 days after virus inoculation reduced viremia and significantly postponed the onset of disease and death by 7 to 10 days. Moreover, MLT injection reduced mortality of SFV (10 PFU) inoculated mice from 100% to 44%. In mice inoculated with high dose of SFV (100 PFU), MLT postponed death and reduced mortality by 20%. In all of the surviving mice anti-SFV antibodies were detected 22 days after virus inoculation. Infection of mice stressed by either isolation or dexamethasone injection with WN-25 induced mortality of 75% and 50% respectively, which was reduced by MLT administration to 31% and 25%, respectively. The efficiency of MLT in protecting from lethal viral infections warrants further investigations on its mechanisms of action.


Blackwell, JL; Brinton, MA. BHK cell proteins that bind to the 3' stem-loop structure of the West Nile virus genome RNA. Journal of Virology. 1995 Sep; 69(9): 5650-8. ISSN: 0022-538X.

NAL Call No.: QR360.J6

Descriptors: 3’nucleotides of WNV RNA, stem-loop structure, RNA replication, uninfected and WNV-infected BHK-21 S100 cytoplasmic extracts, cytoplasmic extracts, cell proteins, cross linking, binding studies.

Abstract: The first 83 3' nucleotides of the genome RNA of the flavivirus West Nile encephalitis virus (WNV) form a stable stem-loop (SL) structure which is followed in the genome by a smaller SL. These 3' structures are highly conserved among divergent flaviviruses, suggesting that they may function as cis-acting signals for RNA replication and as such might specifically bind to cellular or viral proteins. Cellular proteins from uninfected and WNV-infected BHK-21 S100 cytoplasmic extracts formed three distinct complexes with the WNV plus-strand 3' SL [(+)3'SL] RNA in a gel mobility shift assay. Subsequent competitor gel shift analyses showed that two of these RNA-protein complexes, complexes 1 and 2, contained cell proteins that specifically bound to the WNV (+)3'SL RNA. UV-induced cross-linking and Northwestern blotting analyses detected WNV (+)3'SL RNA-binding proteins of 56, 84, and 105 kDa. When the S100 cytoplasmic extracts were partially purified by ion-exchange chromatography, a complex that comigrated with complex 1 was detected in fraction 19, while a complex that comigrated with complex 2 was detected in fraction 17. UV-induced cross-linking experiments indicated that an 84-kDa cell protein in fraction 17 and a 105-kDa protein in fraction 19 bound specifically to the WNV (+)3'SL RNA. In addition to binding to the (+)3'SL RNA, the 105-kDa protein bound to the SL structure located at the 3' end of the WNV minus-strand RNA. Initial mapping studies indicated that the 84- and 105-kDa proteins bind to different regions of the (+)3'SL RNA. The 3'-terminal SL RNA of another flavivirus, dengue virus type 3, specifically competed with the WNV (+)3'SL RNA in gel shift assays, suggesting that the host proteins identified in this study are flavivirus specific.

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February 26, 2003