Increased CD4 and CCR5 expression and human immunodeficiency virus type 1 entry in CD40 ligand-stimulated macrophages.
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.
Bergamini
Alberto
A
Department of Public Health and Cellular Biology, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy. bergamini@med.uniroma2.it
Bolacchi
Francesca
F
Pesce
Caterina Delfina
CD
Carbone
Marica
M
Cepparulo
Mario
M
Demin
Flavio
F
Rocchi
Giovanni
G
D015704:CD4 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000494:pharmacology* / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D019713:Receptors, CCR5 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication
D015704:CD4 Antigens; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D023201:CD40 Ligand