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.
Institute of Virology, University Hospital Rotterdam, 3015 GE Rotterdam, The Netherlands.
M
M
Schutten
C A
CA
van Baalen
C
C
Guillon
R C
RC
Huisman
P H
PH
Boers
K
K
Sintnicolaas
R A
RA
Gruters
A D
AD
Osterhaus
D000818:Animals; D004195:Disease Models, Animal; D015694:Gene Products, rev / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology*; D051379:Mice; D008808:Mice, Inbred CBA; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D054321:rev Gene Products, Human Immunodeficiency Virus