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Journal of Virology, June 2009, p. 5765-5772, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00130-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 gp120 Reprogramming of CD4+ T-Cell Migration Provides a Mechanism for Lymphadenopathy{triangledown}

Daniel S. Green,1,2 David M. Center,1 and William W. Cruikshank1*

The Pulmonary Center,1 Department of Microbiology, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 012282

Received 20 January 2009/ Accepted 9 March 2009

Infection by human immunodeficiency virus type 1 (HIV-1) is associated with decreases in peripheral CD4+ T cells and development of lymphadenopathy. The precise mechanisms by which HIV-1 induces these changes have not been elucidated. T-cell trafficking through lymphoid tissues is facilitated by CCL21-mediated entry and sphingosine-1-phosphate (S1P)-mediated egress. Having previously determined that HIV-1 envelop glycoprotein, gp120, directly alters T-cell migration, we investigated whether gp120 without HIV-1 infection could influence the responses of CD4+ T cells to the signals involved in T-cell trafficking through lymph tissue. Incubation of normal human T cells with gp120 for 1 h resulted in reprogramming of CD4 T-cell migratory responses by increasing sensitivity to CCL20 and CCL21 and complete inhibition of migration to S1P. Incubation of human T cells with gp120 prior to injection into NOD.CB17-Prkdcscid/J mice resulted in increases in lymph node accumulation of CD4+ T cells, with reciprocal decreases in blood and spleen compared to T cells not exposed to gp120. The effects of gp120 required CD4 signaling mediated through p56lck. These findings suggest that gp120 alone can alter CD4+ influx and efflux from lymph nodes in a fashion consistent with the development of lymphopenia and lymphadenopathy.


* Corresponding author. Mailing address: The Pulmonary Center Boston University School of Medicine, 715 Albany St., Boston, MA 01228. Phone: (617) 638-5295. Fax: (617) 536-8093. E-mail: bcruiksh{at}bu.edu

{triangledown} Published ahead of print on 18 March 2009.


Journal of Virology, June 2009, p. 5765-5772, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00130-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.