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Journal of Virology, April 2005, p. 5220-5226, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5220-5226.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Tissue-Resident Macrophages Are Productively Infected Ex Vivo by Primary X4 Isolates of Human Immunodeficiency Virus Type 1

Prerana Jayakumar,1 Irina Berger,2 Frank Autschbach,2 Mark Weinstein,3 Benjamin Funke,2 Eric Verdin,1 Mark A. Goldsmith,1,{dagger} and Oliver T. Keppler1,4*

Gladstone Institute of Virology and Immunology,1 Department of Pathology, San Francisco General Hospital, University of California San Francisco, San Francisco, California,3 Institute of Pathology,2 Department of Virology, University of Heidelberg, Heidelberg, Germany4

Received 2 November 2004/ Accepted 21 November 2004

Infection of macrophages has been implicated as a critical event in the transmission and persistence of human immunodeficiency virus type 1 (HIV-1). Here, we explore whether primary X4 HIV-1 isolates can productively infect tissue macrophages that have terminally differentiated in vivo. Using immunohistochemistry, HIV-1 RNA in situ hybridization, and confocal immunofluorescence microscopy, we demonstrate that macrophages residing in human tonsil blocks can be productively infected ex vivo by primary X4 HIV-1 isolates. This challenges the model in which macrophage tropism is a key determinant of the selective transmission of R5 HIV-1 strains. Infection of tissue macrophages by X4 HIV-1 may be highly relevant in vivo and contribute to key events in HIV-1 pathogenesis.

* Corresponding author. Mailing address: Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany. Phone: 49-6221-565007. Fax: 49-6221-565003. E-mail: oliver_keppler{at}med.uni-heidelberg.de.

{dagger} Present address: Genencor International, Inc., Palo Alto, CA 94304.

Journal of Virology, April 2005, p. 5220-5226, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5220-5226.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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