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Journal of Virology, April 2005, p. 4679-4690, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4679-4690.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Expression of CD154 by a Simian Immunodeficiency Virus Vector Induces Only Transitory Changes in Rhesus Macaques

Vida L. Hodara,1 M. Cristina Velasquillo,1,{dagger} Laura M. Parodi,1 and Luis D. Giavedoni1,2*

Department of Virology and Immunology,1 Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, Texas2

Received 23 June 2004/ Accepted 5 December 2004

Human immunodeficiency virus infection is characterized by dysregulation of antigen-presenting cell function and defects in cell-mediated immunity. Recent evidence suggests that impaired ability of CD4+ T cells to upregulate the costimulatory molecule CD154 is at the core of this dysregulation. To test the hypothesis that increased expression of CD154 on infected CD4+ T cells could modulate immune function, we constructed a replication-competent simian immunodeficiency virus (SIV) vector that expressed CD154. We found that this recombinant vector directed the expression of CD154 on the surface of infected CD4+ T cells and that expression of CD154 resulted in activation of B cells present in the same cultures. Experimental infection of rhesus macaques resulted in very low viral loads for the CD154-expressing virus and the control virus, indicating that expression of CD154 did not result in increased viral replication. Analyses of the anti-SIV immune responses and the phenotype of lymphocytes in blood and lymphoid tissues showed changes that occurred during the acute phase of infection only in animals infected with the CD154-expressing SIV, but that became indistinguishable from those seen in animals infected with the control virus at later time points. We conclude that the level of expression of CD154 in itself is not responsible for affecting the immune response to an attenuated virus. Considering that the CD154-expressing SIV vector and the virus control did not carry an active nef gene, our results suggest that, in CD4+ T cells infected with wild-type virus, Nef is the viral factor that interferes with the immune mechanisms that regulate expression of CD154.

* Corresponding author. Mailing address: Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227. Phone: (210) 258-9603. Fax: (210) 670-3310. E-mail: lgiavedo{at}sfbr.org.

{dagger} Present address: Centro Nacional de Rehabilitación, Xochimilco, C.P.14389, Mexico.

Journal of Virology, April 2005, p. 4679-4690, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4679-4690.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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