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Suppression of Acute Anti-Friend Virus CD8⁺ T-Cell Responses by Coinfection with Lactate Dehydrogenase-Elevating Virus

Shelly J. Robertson,^1, Christoph G. Ammann,^1, Ronald J. Messer,¹ Aaron B. Carmody,¹ Lara Myers,¹ Ulf Dittmer,² Savita Nair,² Nicole Gerlach,² Leonard H. Evans,¹ William A. Cafruny,³ and Kim J. Hasenkrug^1*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,¹ Institute of Virology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany,² Sanford School of Medicine, University of South Dakota, 414 Clark St., Vermillion, South Dakota 57069³

Received 28 June 2007/ Accepted 11 October 2007

Friend virus (FV) and lactate dehydrogenase-elevating virus (LDV) are endemic mouse viruses that can cause long-term chronic infections in mice. We found that numerous mouse-passaged FV isolates also contained LDV and that coinfection with LDV delayed FV-specific CD8⁺ T-cell responses during acute infection. While LDV did not alter the type of acute pathology induced by FV, which was severe splenomegaly caused by erythroproliferation, the immunosuppression mediated by LDV increased both the severity and the duration of FV infection. Compared to mice infected with FV alone, those coinfected with both FV and LDV had delayed CD8⁺ T-cell responses, as measured by FV-specific tetramers. This delayed response accounted for the prolonged and exacerbated acute phase of FV infection. Suppression of FV-specific CD8⁺ T-cell responses occurred not only in mice infected concomitantly with LDV but also in mice chronically infected with LDV 8 weeks prior to infection with FV. The LDV-induced suppression was not mediated by T regulatory cells, and no inhibition of the CD4⁺ T-cell or antibody responses was observed. Considering that most human adults are carriers of chronically infectious viruses at the time of new virus insults and that coinfections with viruses such as human immunodeficiency virus and hepatitis C virus are currently epidemic, it is of great interest to determine how infection with one virus may impact host responses to a second infection. Coinfection of mice with LDV and FV provides a well-defined, natural host model for such studies.

Published ahead of print on 24 October 2007.

S.J.R. and C.G.A. contributed equally to the work described in this article.

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