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Journal of Virology, April 2005, p. 4965-4976, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4965-4976.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Preferential Feline Immunodeficiency Virus (FIV) Infection of CD4+ CD25+ T-Regulatory Cells Correlates both with Surface Expression of CXCR4 and Activation of FIV Long Terminal Repeat Binding Cellular Transcriptional Factors

Anjali Joshi, Himanshu Garg,{dagger} Mary B. Tompkins, and Wayne A. Tompkins*

Immunology Program, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina

Received 11 August 2004/ Accepted 19 November 2004

Previously, we have characterized feline CD4+ CD25+ T-regulatory (Treg) cells with regard to their immune regulatory properties and ability to support feline immunodeficiency virus (FIV) replication in vitro and in vivo. Our studies showed that while CD4+ CD25+ cells were capable of replicating FIV in the presence of interleukin-2 (IL-2) alone, CD4+ CD25– cells harbored a latent infection that required a strong mitogenic stimulus to activate virus replication. In the present study, we investigated the mechanisms governing the preferential replication of FIV in highly purified CD4+ CD25+ Treg cells compared to their CD4+ CD25– counterparts. Studies aimed at elucidating mechanisms regulating infection of these cells revealed that CD4+ CD25– cells were less susceptible to FIV binding and entry than CD4+ CD25+ cells, which correlated with increased surface expression of FIV coreceptor CXCR4. In addition, the number of CD4+ CD25+ cells that expressed the primary receptor CD134 was greater than for CD4+ CD25– cells. Although increased permissiveness to FIV infection of CD4+ CD25– cells following mitogenic stimulation correlated strongly with upregulation of surface CXCR4, it did not correlate with CD134 expression. Further, study of intracellular factors regulating FIV replication revealed that CD4+ CD25+ but not CD4+ CD25– T cells showed constitutive and IL-2-responsive transactivation of activating transcription factor, CAAT enhancer binding protein, and activating protein 1 transcription factors that are important for FIV replication. These factors were upregulated in CD4+ CD25– T cells following ConA stimulation, which correlated with FIV replication. This is the first report elucidating the mechanisms that allow for productive lentiviral infection of CD4+ CD25+ Treg cells.

* Corresponding author. Mailing address: College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St., Raleigh, NC 27606. Phone: (919) 515-7394. Fax: (919) 515-4237. E-mail: Wayne_Tompkins{at}ncsu.edu.

{dagger} Present address: National Cancer Institute, Frederick, MD 21702.

Journal of Virology, April 2005, p. 4965-4976, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4965-4976.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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