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Increased CD4 and CCR5 Expression and Human Immunodeficiency Virus Type 1 Entry in CD40 Ligand-Stimulated Macrophages

Alberto Bergamini, Francesca Bolacchi, Caterina Delfina Pesce, Marica Carbone, Mario Cepparulo, Flavio Demin and Giovanni Rocchi
The Journal of Infectious Diseases
Vol. 185, No. 11 (Jun. 1, 2002), pp. 1567-1577
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30138091
Page Count: 11
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Increased CD4 and CCR5 Expression and Human Immunodeficiency Virus Type 1 Entry in CD40 Ligand-Stimulated Macrophages
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Abstract

The effects of a soluble trimeric CD40 ligand (CD40L) agonist on the expression of CD4 and CCR5 and on human immunodeficiency virus (HIV) type 1 entry into and replication in human macrophages were investigated. CD40L increased the number of CD4 and CCR5 antibody-binding sites and the percentage of CD4⁻ and CCR5-expressing cells. Infection of CD40L-stimulated macrophages with HIV-1 resulted in a marked increase of viral DNA with respect to controls, as demonstrated by polymerase chain reaction assay. HIV-1 p24 antigen analysis showed that peak viral production did not differ between CD40L-stimulated macrophages and controls. However, because of a prolonged life span, overall viral output was increased in CD40L-stimulated cultures. In addition, CD40L down-regulated the antiviral efficacy of compounds that inhibit HIV-1 reverse transcriptase. In conclusion, CD40L stimulation of macrophages can contribute to plasma virus load and favor the establishment of a pool of latently infected macrophages that can be reactivated to release virus.

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