HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Smith, C. Articles by Efstathiou, S. Search for Related Content PubMed PubMed Citation Articles by Smith, C. Articles by Efstathiou, S. Agricola Articles by Smith, C. Articles by Efstathiou, S.

Expression from the herpes simplex virus type 1 latency-associated promoter in the murine central nervous system

Division of Virology, Dept of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK¹

Author for correspondence: Stacey Efstathiou. Fax +44 1223 336926. e-mail se{at}mole.bio.cam.ac.uk

Herpes simplex virus type 1 (HSV-1) establishes latency in neurones of both the central (CNS) and peripheral nervous system and can be used to drive long-term expression of the lacZ reporter gene by insertion of an encephalomyocarditis virus IRES-linked gene 1·5 kb downstream of the latency-associated transcript (LAT) start site. However, the kinetics of LAT promoter (LAP) activity, and its ability to function in all neuronal types within the CNS has not been studied in detail. In order to address these issues, mice were infected via the ear pinna with 2x10⁶ p.f.u. of either SC16-LA, which contains an IRES-linked lacZ under the control of LAP, or SC16-C3b, which expresses LacZ under the control of the human cytomegalovirus immediate early (HCMV-IE) promoter. Three to five animals from each group were sampled over a time-course from 5 days to 1 year post-infection (p.i.), and brainstem and spinal cord sections were examined histochemically for LacZ expression. We found that HCMV-IE promoter activity could be detected within distinct CNS regions from 5 to 15 days p.i. In contrast, LAP-driven LacZ expression was first detected at 7 days p.i. and persisted for at least 1 year. At times up to 34 days p.i., LAP activity was seen in similar regions of the CNS as those which were positive for HCMV-IE promoter activity during the acute stage of infection. After 34 days, however, the numbers of cells in which the LAP was active decreased and labelled motorneurones were predominantly detected in the facial and hypoglossal nuclei and occasionally also in the ventral spinal cord. These results suggest that following the establishment of latency in the CNS, the efficiency of long-term LAP-mediated gene expression may be influenced by the neuronal cell type in which latency is established.

This article has been cited by other articles:

				J. T. Proenca, H. M. Coleman, V. Connor, D. J. Winton, and S. Efstathiou A historical analysis of herpes simplex virus promoter activation in vivo reveals distinct populations of latently infected neurones J. Gen. Virol., December 1, 2008; 89(12): 2965 - 2974. [Abstract] [Full Text] [PDF]

				M. Labetoulle, S. Maillet, S. Efstathiou, S. Dezelee, E. Frau, and F. Lafay HSV1 Latency Sites after Inoculation in the Lip: Assessment of their Localization and Connections to the Eye Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 217 - 225. [Abstract] [Full Text] [PDF]