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Journal of Virology, October 1999, p. 7972-7980, Vol. 73, No. 10
0022-538X/99/$04.00+0

CD40-Mediated Induction of CD4 and CXCR4 on B Lymphocytes Correlates with Restricted Susceptibility to Human Immunodeficiency Virus Type 1 Infection: Potential Role of B Lymphocytes as a Viral Reservoir

Susan Moir,1,* Réjean Lapointe,2 Angela Malaspina,1 Mario Ostrowski,1 Charsey E. Cole,1 Tae-Wook Chun,1 Joseph Adelsberger,3 Michael Baseler,3 Patrick Hwu,2 and Anthony S. Fauci1

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases,1 and Surgery Branch, National Cancer Institute,2 National Institutes of Health, Bethesda, Maryland 20892, and SAIC/Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 217023

Received 17 December 1998/Accepted 22 June 1999

Human immunodeficiency virus type 1 (HIV-1) replicates primarily in lymphoid tissues where it has ready access to activated immune competent cells. We used one of the major pathways of immune activation, namely, CD40-CD40L interactions, to study the infectability of B lymphocytes isolated from peripheral blood mononuclear cells. Highly enriched populations of B lymphocytes generated in the presence of interleukin-4 and oligomeric soluble CD40L upregulated costimulatory and activation markers, as well as HIV-1 receptors CD4 and CXCR4, but not CCR5. By using single-round competent luciferase viruses complemented with either amphotropic or HIV-derived envelopes, we found a direct correlation between upregulation of HIV-1 receptors and the susceptibility of the B lymphocytes to infection with dual-tropic and T-tropic strains of HIV-1; in contrast, cells were resistant to M-tropic strains of HIV-1. HIV-1 envelope-mediated infection was completely abolished with either an anti-CD4 monoclonal antibody or a peptide known to directly block CXCR4 usage and partially blocked with stromal cell-derived factor 1, all of which had no effect on the entry of virus pseudotyped with amphotropic envelope. Full virus replication kinetics confirmed that infection depends on CXCR4 usage. Furthermore, productive cycles of virus replication occurred rapidly yet under most conditions, without the appearance of syncytia. Thus, an activated immunological environment may induce the expression of HIV-1 receptors on B lymphocytes, priming them for infection with selective strains of HIV-1 and allowing them to serve as a potential viral reservoir.

* Corresponding author. Mailing address: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., MSC-1576, Bldg. 10, Rm. 6A02, Bethesda, MD 20892. Phone: (301) 402-4559. Fax: (301) 402-4122. E-mail: smoir{at}niaid.nih.gov.

Journal of Virology, October 1999, p. 7972-7980, Vol. 73, No. 10
0022-538X/99/$04.00+0


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