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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-08-2653.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1684-1691
CHEMOKINES
Simian immunodeficiency virus dramatically alters expression of
homeostatic chemokines and dendritic cell markers during infection
in vivo
Yang Kyu Choi,
Beth
A. Fallert,
Michael A. Murphey-Corb, and
Todd A. Reinhart
From the Department of Infectious Diseases and
Microbiology and the Department of Molecular Genetics and Biochemistry,
University of Pittsburgh, PA.
Dendritic cells (DCs) are potent antigen-presenting cells
that likely play multiple roles in human immunodeficiency virus type 1 (HIV-1) pathogenesis. We used the simian immunodeficiency virus
(SIV)/macaque model to study the effects of infection on homeostatic
chemokine expression and DC localization directly in secondary lymphoid
tissues. SIV infection altered the expression of chemokines
(CCL19/MIP-3 , CCL21/ 6Ckine, and CCL20/MIP-3 ) and of chemokine
receptors (CCR7 and CCR6) that drive DC trafficking. CCL19/MIP-3 ,
CCL20/MIP-3 , CCR6, and CCR7 expression increased in lymph nodes
during the early systemic burst of viral replication (acute infection),
whereas CCL21/6Ckine expression progressively decreased throughout
disease to AIDS. Parallel with the SIV-induced perturbations in
chemokine expression were changes in the expression of the
DC-associated markers, DC-SIGN, DC-LAMP, and DECTIN-1. During AIDS,
DC-LAMP mRNA expression levels were significantly reduced in lymph
nodes and spleen, and DC-SIGN levels were significantly reduced in
spleen. These findings suggest that the disruption of homeostatic
chemokine expression is responsible, in part, for alterations in the
networks of antigen-presenting cells in lymphoid tissues, ultimately
contributing to systemic immunodeficiency.

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