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Journal of Virology, October 2002, p. 9787-9797, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9787-9797.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Increased Macrophage Infection upon Subcutaneous Inoculation of Rhesus Macaques with Simian Immunodeficiency Virus-Loaded Dendritic Cells or T Cells but Not with Cell-Free Virus

Ralf Ignatius,1,{dagger} Klara Tenner-Racz,2 Davorka Messmer,1,{ddagger} Agegnehu Gettie,3 James Blanchard,4 Amara Luckay,3 Christine Russo,3 Stephen Smith,5 Preston A. Marx,3,4 Ralph M. Steinman,1 Paul Racz,2 and Melissa Pope1*

Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021,1 Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany,2 The Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016,3 Tulane Regional Primate Research Center, Covington, Louisiana 70433,4 St. Michael's Medical Center and The New Jersey Medical School, Newark, New Jersey 071025

Received 3 April 2002/ Accepted 18 June 2002

Information on the establishment of immunodeficiency virus infection through transmission of infected cells is sparse. Dendritic cells (DCs) and T cells may be central to the onset and subsequent spread of infection following mucosal exposure. To directly investigate the consequences of virus being introduced by DCs or T cells, we reinjected ex vivo simian immunodeficiency virus (SIV)-loaded autologous immature DCs and T cells subcutaneously (s.c.) into healthy macaques. s.c. injection of cell-bound virus was used to mirror what may happen if virus-loaded cells pass through an epithelium or perhaps DCs and T cells that immediately entrap cell-free virus, having just crossed an epithelial barrier. Virus load in the plasma was monitored along with combined in situ hybridization and immunohistochemistry to identify the cells replicating virus in the lymphoid tissues. Both DCs and T cells transmitted infection after being pulsed with either wild-type or nef-defective (delta nef) SIVmac239. As seen in animals infected intravenously, replication of delta nef was attenuated compared to that of wild-type virus when introduced in either cell-bound form. Upon examination of the draining lymph nodes (LNs) during the first days of infection, virus-producing CD4+ T cells predominated in control animals that received s.c. cell-free virus. In dramatic contrast, both SIV-positive macrophages and T cells were detected in the LNs of monkeys infected with cell-associated SIV. Therefore, although both cell-free and cell-associated viruses are infectious, the initial cells amplifying the virus differ. This may have important implications for the subsequent dissemination of infection and/or induction of antiretroviral immunity.

* Corresponding author. Present address: Center for Biomedical Research, Population Council, 1230 York Ave., New York, NY 10021. Phone: (212) 327-7794. Fax: (212) 327-7764. E-mail: mpope{at}popcbr.rockefeller.edu.

{dagger} Present address: Department of Medical Microbiology and Immunology of Infection, Benjamin Franklin Medical Center, Free University of Berlin, D-12203 Berlin, Germany.

{ddagger} Present address: Department of Experimental Immunology, North Shore Long Island Jewish Research Institute, Manhasset, NY 11030.

Journal of Virology, October 2002, p. 9787-9797, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9787-9797.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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