Nef expands HIV-1 cellular reservoir

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 Nature, Simon Swingler and colleagues at the University of Massachusetts Medical School show that Nef expands the cellular reservoir of HIV-1 by permitting the infection of resting T lymphocytes (Nature, 424:213-219, July 10, 2003).

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 lymphocytes stimulated ...