The cell tropism of human immunodeficiency virus type 1 determines the kinetics of plasma viremia in SCID mice reconstituted with human peripheral blood leukocytes

Most individuals infected with human immunodeficiency virus type 1 (HIV-1) initially harbor macrophage-tropic, non-syncytium-inducing (M-tropic, NSI) viruses that may evolve into T-cell-tropic, syncytium- inducing viruses (T-tropic, SI) after several years. The reasons for the more efficient transmission of hi-tropic, NSI viruses and the slow evolution of T-tropic, SI viruses remain unclear, although they may be linked to expression of appropriate chemokine coreceptors for virus entry, We have examined plasma viral RNA levels and the extent of CD4(+) T-cell depletion in SCID mice reconstituted with human peripheral blood leukocytes following infection with hi-tropic, dual-tropic, or T-tropic HIV-1 isolates, The cell tropism was found to determine the course of viremia, with hi-tropic viruses producing sustained high viral RNA levels and sparing some CD4(+) T cells, dual-tropic viruses producing a transient and lon er viral RNA spike and extremely rapid depletion of CD4(+) T cells, and T-tropic viruses causing similarly lower viral RNA levels and rapid intermediate rates of CD4(+) T-cell depletion, A single amino acid change in the V3 region of gp120 was sufficient to cause one isolate to snitch from hi-tropic to dual-tropic and acquire the ability to rapidly deplete all CD4(+) T cells.