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Journal of Virology, March 2007, p. 2297-2306, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01795-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Preferential Infection of Dendritic Cells during Human Immunodeficiency Virus Type 1 Infection of Blood Leukocytes{triangledown}

Paul U. Cameron,1,3* Amanda J. Handley,4 Dean C. Baylis,4 Ajantha E. Solomon,2 Nicholas Bernard,4 Damian F. J. Purcell,4 and Sharon R. Lewin2,3

Department of Immunology,1 Department of Medicine, Monash University, Commercial Rd., Melbourne 3004, Australia,2 Infectious Diseases Unit, Alfred Hospital, Department of Medicine, Monash University, Commercial Rd., Melbourne 3004, Australia,3 Department of Microbiology and Immunology, University of Melbourne, Grattan St., Parkville, Victoria 3052, Australia4

Received 17 August 2006/ Accepted 5 December 2006

Human immunodeficiency virus type 1 (HIV-1) transmission by the parenteral route is similar to mucosal transmission in the predominance of virus using the CCR5 coreceptor (R5 virus), but it is unclear whether blood dendritic cells (DCs), monocytes, or T cells are the cells initially infected. We used ex vivo HIV-1 infection of sorted blood mononuclear cells to model the in vivo infection of blood leukocytes. Using quantitative real-time PCR to detect full-length HIV-1 DNA, both sorted CD11c+ myeloid and CD11c– plasmacytoid DCs were more frequently infected than other blood mononuclear cells, including CD16+ or CD14+ monocytes or resting CD4+ T cells. There was a strong correlation between CCR5 coreceptor use and preferential DC infection across a range of HIV-1 isolates. After infection of unsorted blood mononuclear cells, HIV-1 was initially detected in the CD11c+ DCs and later in other leukocytes, including clustering DCs and activated T cells. DC infection with R5 virus was productive, as shown by efficient transmission to CD4+ T cells in coculture. Blood DCs infected with HIV-1 in vitro and cultured alone expressed only low levels of multiply spliced HIV-1 RNA unless cocultured with CD4+ T cells. Early selective infection of immature blood DCs by R5 virus and upregulation of viral expression during DC-T-cell interaction and transmission provide a potential pathway for R5 selection following parenteral transmission.

* Corresponding author. Mailing address: Department of Immunology, Monash University, Commercial Rd., Melbourne, Victoria 3004, Australia. Phone: 613 9207 1449. Fax: 613 9276 1340. E-mail: paul.cameron{at}med.monash.edu.au.

{triangledown} Published ahead of print on 13 December 2006.

Journal of Virology, March 2007, p. 2297-2306, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01795-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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