HIV-1 readily invades actively replicating T cells, but it has also been suggested that low levels of intercellular signaling molecules are sufficient for HIV-1 to infect resting human T cells. Nef proteins are important for viral replication and pathogenicity in vivo, but their role in HIV-1 infection of resting cells has been unclear. In the July 10
Swingler et al. examined the ability of peripheral blood lymphocytes to support viral (HIV-1LAI) replication after incubation with macrophages harboring a wildtype (HIV-1SFIWT) or DNef virus (HIV-1SFI DNef). They observed that macrophages that expressed Nef or that were stimulated through the CD40 receptor released a paracrine factor that rendered T lymphocytes permissive to HIV-1 infection, and T...