Interleukin-16 inhibits human immunodeficiency virus type 1 entry and replication in macrophages and in dendritic cells.
Recombinant interleukin-16 (rIL-16) has been found to inhibit human immunodeficiency virus type 1 (HIV-1) replication in acutely or endogenously infected CD4(+) T cells. However, the effect of rIL-16 on HIV-1 replication in antigen-presenting cells (APCs) is still unknown. We show here a potent HIV-suppressive activity of rIL-16 in acutely infected monocyte-derived macrophages and dendritic cells determined by the levels of viral RNA transcripts or of viral reverse transcriptase in culture supernatants. The observed effect was dependent on the presence of rIL-16 early after infection and could not be induced by a 24-h treatment of cells with the cytokine prior to infection. Using macrophage-tropic and dually tropic primary isolates, we also showed that the addition of rIL-16 to cell cultures only during the infection period was effective in blocking virus entry and reducing proviral DNA levels in APCs. However, the anti-HIV activity of rIL-16 could not be linked to the induction of virus-suppressive concentrations of beta-chemokines or to the inhibition of HIV-enhancing cytokines. These findings establish a critical role for rIL-16 in protecting APCs against HIV-1 infection and lend further support to its potential use in the treatment of HIV disease.
Truong
M J
MJ
Institut Pasteur de Lille, INSERM U167, 59019 Lille Cedex, France.
Darcissac
E C
EC
Hermann
E
E
Dewulf
J
J
Capron
A
A
Bahr
G M
GM
D054407:Chemokine CCL4; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000187:drug effects; D003713:Dendritic Cells / Q000821:virology*; D015870:Gene Expression; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D019410:Interleukin-16 / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008264:Macrophages / Q000821:virology*; D011533:Proviruses / Q000235:genetics; D012333:RNA, Messenger; D012367:RNA, Viral / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D054407:Chemokine CCL4; D016207:Cytokines; D004279:DNA, Viral; D019410:Interleukin-16; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins