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Inhibition of herpes simplex virus replication and protein synthesis by non-smoked tobacco, tobacco alkaloids and nitrosamines
Department of Oral Surgery, University of Göteborg, S-413 46 Göteborg, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Medical Genetics. (Research Unit of Replication Enzymology, BMC)
1992 (English)In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 37, no 11, 969-978 p.Article in journal (Refereed) Published
Abstract [en]

Inhibitory effects of snuff extract and the tobacco chemicals nicotine, anabasine, diethyl-N-nitrosamine (DEN), and the tobacco-specific nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on herpes simplex virus type 1 (HSV-1) replication in vitro and on HSV-1 protein synthesis in infected cells were analysed. Snuff extract and nicotine caused a significant reduction of HSV-1 attachment to cell membranes whereas anabasine, DEN, NNN and NNK did not affect adsorption of HSV-1. Virus production assays in the presence of snuff added after virus adsorption resulted in a significantly reduced production of virus at low multiplicities of infection (MOI), but at high MOI the inhibitory effect of snuff extract was less pronounced. DEN, NNN and NNK only affected virus production at toxic concentrations. Nicotine and anabasine reduced virus production in non-toxic doses but not at the concentrations present in snuff extract. In HSV-infected cells exposed to snuff extract, the immediate early (α-) infected cell proteins (ICPs) 4 and 27 (as well as the early (β-) ICPs 6 and 8) were markedly increased, whereas the late (γ-) ICPs 5, 11 and 29 were reduced. Nicotine had a less pronounced stimulating effect on the production of α-proteins but no detectable effect on production of β- or -γ-proteins. Anabasine, DEN, NNN and NNK did not affect HSV protein synthesis at non-toxic concentrations. Synthesis of thymidine kinase and DNA polymerase was significantly reduced by snuff extract. Also nicotine and anabasine affected thymidine kinase and DNA polymerase but only at toxic concentrations. The production of the cellular protein actin, which almost disappears a few hours after HSV-1 infection, remained at a significant level in HSV-infected cells exposed to snuff. Thus snuff extract blocks the replicative cycle of HSV at an early stage, which results in an increased production of α-proteins in the infected cells and in prolonged maintenance of cellular functions. This may be of importance for HSV-induced transformation and the development of HSV-associated tumours.

Place, publisher, year, edition, pages
1992. Vol. 37, no 11, 969-978 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-222055DOI: 10.1016/0003-9969(92)90069-KPubMedID: 1334651OAI: oai:DiVA.org:uu-222055DiVA: diva2:710605
Available from: 2014-04-07 Created: 2014-04-07 Last updated: 2014-11-04Bibliographically approved

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