Macrophage tropism of human immunodeficiency virus type 1 facilitates in vivo escape from cytotoxic T-lymphocyte pressure

Early after seroconversion, macrophage-tropic human immunodeficiency virus type 1 (HIV-1) variants are predominantly found, even when a mixture of mac rophage-tropic and non-macrophage-tropic variants was transmitted. For viru s contracted by sexual transmission, this is presently explained by selecti on at the port of entry, where macrophages are infected and T cells are rel atively rare. Here we explore an additional mechanism to explain the select ion of macrophage-tropic variants in cases where the mucosa is bypassed dur ing transmission, such as blood transfusion, needle-stick accidents, or int ravenous drug abuse. with molecularly cloned primary isolates of HIV-1 in i rradiated mice that had been reconstituted with a high dose of human periph eral blood mononuclear cells, we found that a macrophage-tropic HIV-1 clone escaped more efficiently from specific cytotoxic T-lymphocyte (CTL) pressu re than its non-macrophage-tropic counterpart. We propose that CTLs favor t he selective outgrowth of macrophage-tropic HIV-1 variants because infected macrophages are less susceptible to CTL activity than infected T cells.