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Journal of Virology, November 2007, p. 11881-11890, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01554-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Level of Friend Retrovirus Replication Determines the Cytolytic Pathway of CD8+ T-Cell-Mediated Pathogen Control{triangledown}

Gennadiy Zelinskyy,1* Sandra Balkow,2 Simone Schimmer,1 Tanja Werner,1 Markus M. Simon,2 and Ulf Dittmer1

Institut für Virologie des Universitätsklinikums Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany,1 Max Plank-Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany2

Received 17 July 2007/ Accepted 20 August 2007

Cytotoxic T cells (CTL) play a central role in the control of viral infections. Their antiviral activity can be mediated by at least two cytotoxic pathways, namely, the granule exocytosis pathway, involving perforin and granzymes, and the Fas-FasL pathway. However, the viral factor(s) that influences the selection of one or the other pathway for pathogen control is elusive. Here we investigate the role of viral replication levels in the induction and activation of CTL, including their effector potential, during acute Friend murine leukemia virus (F-MuLV) infection. F-MuLV inoculation results in a low-level infection of adult C57BL/6 mice that is enhanced about 500-fold upon coinfection with the spleen focus-forming virus (SFFV). Both the low- and high-level F-MuLV infections generated CD8+ effector T cells that were essential for the control of viral replication. However, the low-level infection induced CD8+ T cells expressing solely FasL but not the cytotoxic molecules granzymes A and B, whereas the high-level infection resulted in induction of CD8+ effector T cells secreting molecules of the granule exocytosis pathway. By using knockout mouse strains deficient in one or the other cytotoxic pathway, we found that low-level viral replication was controlled by CTL that expressed FasL but control of high-level viral replication required perforin and granzymes. Additional studies, in which F-MuLV replication was enhanced experimentally in the absence of SFFV coinfection, supported the notion that only the replication level of F-MuLV was the critical factor that determined the differential expression of cytotoxic molecules by CD8+ T cells and the pathway of CTL cytotoxicity.

* Corresponding author. Mailing address: Institut für Virologie, des Universitätsklinikums Essen, Hufelandstr. 55, 45122 Essen, Germany. Phone: 49-201-723 3693. Fax: 49-201-723 5929. E-mail: ulf.dittmer{at}uni-due.de

{triangledown} Published ahead of print on 29 August 2007.

Journal of Virology, November 2007, p. 11881-11890, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01554-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zelinskyy, G., Dietze, K. K., Husecken, Y. P., Schimmer, S., Nair, S., Werner, T., Gibbert, K., Kershaw, O., Gruber, A. D., Sparwasser, T., Dittmer, U. (2009). The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response. Blood 114: 3199-3207 [Abstract] [Full Text]  


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