Background:  Several B-cell abnormalities are seen following infection with HIV-1. However, the exact mechanisms of B-cell dysfunction during HIV-1 infection are poorly understood. Having recently shown that CD40L, the ligand for CD40, is inserted within budding HIV-1 particles, we hypothesized that the contact between virus-anchored host CD40L and CD40 on the surface of B lymphocytes might result in activation of this cell type. Moreover, we wondered whether this additional interaction between HIV-1 and B cells might facilitate an eventual virus transfer to more susceptible target cells such as autologous CD4⁺ T lymphocytes.

Methods:  Autologous B cells and CD4⁺ T lymphocytes were isolated from human tonsils. Isogenic virions either lacking (NL4-3/null) or bearing CD40L (NL4-3/CD40L) were produced by transient transfection of 293T cells. Virus preparations were incubated first with purified B cells before performing virus binding, electrophoretic mobility shift and transmission assays.

Results:  Attachment of NL4-3/CD40L virions to B lymphocytes was augmented compared to isogenic NL4-3/null viruses. Moreover, NL4-3 particles bearing CD40L, but not viruses lacking host CD40L, induced the nuclear translocation of NF-kB in B lymphocytes. The presence of host-derived CD40L within HIV-1 envelope resulted in an enhanced infection of CD4⁺ T cells in trans upon co-culture with B lymphocytes.

Conclusions:  Altogether the data gathered from this series of investigations suggest that incorporation of host-encoded CD40L in HIV-1 might play a role in the described B-cell abnormalities seen in infected individuals.