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Journal of Virology, November 2009, p. 11211-11222, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01225-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Race between Retroviral Spread and CD4+ T-Cell Response Determines the Outcome of Acute Friend Virus Infection{triangledown}

Rebecca Pike,1 Andrew Filby,1 Mickaël J.-Y. Ploquin,1 Urszula Eksmond,1 Rute Marques,1 Inês Antunes,1 Kim Hasenkrug,2 and George Kassiotis1*

Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom,1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 598402

Received 14 June 2009/ Accepted 10 August 2009

Retroviruses can establish persistent infection despite induction of a multipartite antiviral immune response. Whether collective failure of all parts of the immune response or selective deficiency in one crucial part underlies the inability of the host to clear retroviral infections is currently uncertain. We examine here the contribution of virus-specific CD4+ T cells in resistance against Friend virus (FV) infection in the murine host. We show that the magnitude and duration of the FV-specific CD4+ T-cell response is directly proportional to resistance against acute FV infection and subsequent disease. Notably, significant protection against FV-induced disease is afforded by FV-specific CD4+ T cells in the absence of a virus-specific CD8+ T-cell or B-cell response. Enhanced spread of FV infection in hosts with increased genetic susceptibility or coinfection with Lactate dehydrogenase-elevating virus (LDV) causes a proportional increase in the number of FV-specific CD4+ T cells required to control FV-induced disease. Furthermore, ultimate failure of FV/LDV coinfected hosts to control FV-induced disease is accompanied by accelerated contraction of the FV-specific CD4+ T-cell response. Conversely, an increased frequency or continuous supply of FV-specific CD4+ T cells is both necessary and sufficient to effectively contain acute infection and prevent disease, even in the presence of coinfection. Thus, these results suggest that FV-specific CD4+ T cells provide significant direct protection against acute FV infection, the extent of which critically depends on the ratio of FV-infected cells to FV-specific CD4+ T cells.

* Corresponding author. Mailing address: Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 2088 162 354. Fax: 44 2088 162 564. E-mail: gkassio{at}nimr.mrc.ac.uk

{triangledown} Published ahead of print on 19 August 2009.

Journal of Virology, November 2009, p. 11211-11222, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01225-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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