‘Self-Protection’ of Individual CD4 ⁺ T Cells against R5 HIV-1 Infection by the Synthesis of Anti-Viral CCR5 Ligands

Abstract

It is well established that paracrine secretion of anti-viral CCR5 ligands by CD8 ⁺ and CD4 ⁺ T cells can block the infection of activated CD4 ⁺ T cells by R5 and dual-tropic isolates of HIV-1. By contrast, because CD4 ⁺ T cells can be infected by HIV-1 and at least some subsets secrete anti-viral CCR5 ligands, it is possible that these ligands protect against HIV-1 via autocrine as well as paracrine pathways. Here we use a model primary CD4 ⁺ T cell response in vitro to show that individual CD4 ⁺ T cells that secrete anti-viral CCR5 ligands are ‘self-protected’ against infection with R5 but not X4 strains of HIV-1. This protection is selective for CD4 ⁺ T cells that secrete anti-viral CCR5 ligands in that activated CD4 ⁺ T cells in the same cultures remain infectable with R5 HIV-1. These data are most consistent with an autocrine pathway of protection in this system and indicate a previously unappreciated selective pressure on the emergence of viral variants and CD4 ⁺ T cell phenotypes during HIV-1 infection.