Human immunodeficiency virus type 1-anchored CD40 ligand induces secretion of the chemokine interleukin-8 by human primary macrophages.

CD40 ligand (CD40L) is mainly expressed in activated CD4(+)T cells and interacts with CD40 on antigen-presenting cells to regulate both humoral and cellular immune responses. We previously reported that CD40L is acquired by emerging HIV-1 particles. Here we demonstrate that both wild-type and a non-functional mutated form of CD40L are incorporated within HIV-1. Importantly, we show that wild-type CD40L remains functional since CD40L-bearing virions mediate NF-kappaB activation in a CD40-expressing reporter cell line and induce secretion of the chemokine IL-8 by monocyte-derived macrophages. These results suggest a possible means exploited by HIV-1 to attract susceptible target cells to the site of infection, a process that might promote viral dissemination.