This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Barreca, C.
Right arrow Articles by O'Hare, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barreca, C.
Right arrow Articles by O'Hare, P.

 Previous Article  |  Next Article 

Journal of Virology, August 2004, p. 8641-8653, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8641-8653.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Suppression of Herpes Simplex Virus 1 in MDBK Cells via the Interferon Pathway

Cristina Barreca and Peter O'Hare*

Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom

Received 25 February 2004/ Accepted 29 April 2004

Herpes simplex virus (HSV) normally undergoes productive infection in culture, causing cell destruction and plaque formation. Here we characterize an unusual pattern of HSV type 1 (HSV-1) infection in MDBK cells which surprisingly results in suppression of replication, cell recovery, and maintenance of virus. Compared to Vero cells, MDBK cells supported a normal productive infection at a high multiplicity with complete cell destruction. At low multiplicity, HSV also showed an identical initial specific infectivity in the two cell types. Thereafter, the progression of infection was radically different. In contrast to the rapid plaque expansion and eventual destruction in Vero monolayers, in MDBK cells, after initial plaque formation, plaque size actually decreased and, with time, monolayers recovered. Using a green fluorescent protein (GFP)-VP16-expressing virus, we monitored infection in live individual plaques. After early stages of intense GFP-VP16 expression, expression regressed to a thin boundary at the edge of the plaques and was completely suppressed by 10 days. Cells lacking expression then began to grow into the plaque boundaries. Furthermore, following media replacement, individual cells expressing GFP-VP16 could be observed reinitiating infection. The results indicated the production of a potent inhibitory component during infection in MDBK cells, and we show the continued and prolonged presence of interferon in the medium, at times when there was no longer evidence of ongoing productive infection. We exploited the ability of V protein of simian virus 5 to degrade Stat1 and prevent interferon signaling. We established MDBK cells constitutively expressing the V protein with the resultant loss of Stat1. In comparison to the parental cells, infection in these cells now progressed at a rapid rate with expanding plaque formation. We believe the conclusions have significant implications for the study of HSV-1 and interferon signaling both in culture and in animal models.

* Corresponding author. Mailing address: Marie Curie Research Institute, Oxted, The Chart, Surrey RH8 0TL, United Kingdom. Phone: 44 1 88 3722306. Fax: 44 1 88 3714375. E-mail: P.OHare{at}mcri.ac.uk.

Journal of Virology, August 2004, p. 8641-8653, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8641-8653.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de Jong, M. A. W. P., de Witte, L., Bolmstedt, A., van Kooyk, Y., Geijtenbeek, T. B. H. (2008). Dendritic cells mediate herpes simplex virus infection and transmission through the C-type lectin DC-SIGN. J. Gen. Virol. 89: 2398-2409 [Abstract] [Full Text]  
  • Hayman, A., Comely, S., Lackenby, A., Hartgroves, L. C. S., Goodbourn, S., McCauley, J. W., Barclay, W. S. (2007). NS1 Proteins of Avian Influenza A Viruses Can Act as Antagonists of the Human Alpha/Beta Interferon Response. J. Virol. 81: 2318-2327 [Abstract] [Full Text]  
  • Duan, R., Remeijer, L., van Dun, J. M., Osterhaus, A. D. M. E., Verjans, G. M. G. M. (2007). Granulocyte Macrophage Colony-Stimulating Factor Expression in Human Herpetic Stromal Keratitis: Implications for the Role of Neutrophils in HSK. IOVS 48: 277-284 [Abstract] [Full Text]  
  • Howat, T. J, Barreca, C., O'Hare, P., Gog, J. R, Grenfell, B. T (2006). Modelling dynamics of the type I interferon response to in vitro viral infection. J R Soc Interface 3: 699-709 [Abstract] [Full Text]  
  • Barreca, C., O'Hare, P. (2006). Characterization of a potent refractory state and persistence of herpes simplex virus 1 in cell culture.. J. Virol. 80: 9171-9180 [Abstract] [Full Text]  
  • Hohle, C., Karger, A., Konig, P., Giesow, K., Keil, G. M. (2005). High-level expression of biologically active bovine alpha interferon by Bovine herpesvirus 1 interferes only marginally with recombinant virus replication in vitro. J. Gen. Virol. 86: 2685-2695 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»