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

J Virol. 2001 Mar;75(6):2706-9. doi: 10.1128/JVI.75.6.2706-2709.2001.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Products, rev / immunology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / virology
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Macrophages / virology*
  • Mice
  • Mice, Inbred CBA
  • Mutation
  • T-Lymphocytes, Cytotoxic / immunology*
  • Virus Replication
  • rev Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, rev
  • rev Gene Products, Human Immunodeficiency Virus