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 macrophage-tropic and non-macrophage-tropic variants was transmitted. For virus contracted by sexual transmission, this is presently explained by selection at the port of entry, where macrophages are infected and T cells are relatively rare. Here we explore an additional mechanism to explain the selection of macrophage-tropic variants in cases where the mucosa is bypassed during transmission, such as blood transfusion, needle-stick accidents, or intravenous drug abuse. With molecularly cloned primary isolates of HIV-1 in irradiated mice that had been reconstituted with a high dose of human peripheral blood mononuclear cells, we found that a macrophage-tropic HIV-1 clone escaped more efficiently from specific cytotoxic T-lymphocyte (CTL) pressure than its non-macrophage-tropic counterpart. We propose that CTLs favor the selective outgrowth of macrophage-tropic HIV-1 variants because infected macrophages are less susceptible to CTL activity than infected T cells.
|Keywords||Animals, Disease Models, Animal, Gene Products, rev/immunology, Graft vs Host Disease/immunology/virology, HIV Infections/immunology/*virology, HIV-1/genetics/*physiology, Humans, Leukocytes, Mononuclear/virology, Macrophages/*virology, Mice, Mice, Inbred CBA, Mutation, Research Support, Non-U.S. Gov't, T-Lymphocytes, Cytotoxic/*immunology, Virus Replication|
|Note||Free full text at PubMed|
|Persistent URL||dx.doi.org/10.1128/JVI.75.6.2706-2709.2001, hdl.handle.net/1765/12918|
Schutten, M., van Baalen, C.A., Guillon, C., Huisman, R.C., Boers, P.H.M., Sintnicolaas, K., … Osterhaus, A.D.M.E.. (2001). Macrophage tropism of human immunodeficiency virus type 1 facilitates in vivo escape from cytotoxic T-lymphocyte pressure.. Journal of Virology, 75(6), 2706–2709. doi:10.1128/JVI.75.6.2706-2709.2001