HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain

Abstract

CELLS of the mononuclear phagocyte system are the predominant cell producing HIV-1 in most tissues, including the central nervous system (CNS)1–4, spinal cord5, lung6 and skin7,8; infection is associated with dementia9,10, neuropathy11–13, pneumonitis9,14 and dermatitis15,16 respectively. Different HIV-1 isolates vary markedly in their ability to infect mononuclear phagocytes productively17,18. Here we describe molecular clones of a CNS-derived isolate, HIV-1JR–FL which can replicate efficiently in mononuclear phagocytes. Analysis by polymerase chain reaction of early events after infection indicates that the early phase of viral replication before reverse transcription determines tropism. Genetic mapping of the macrophage-tropic phenotype by construction of recombinant viruses indicates that mononuclear phagocyte infectivity can be determined by a 157-amino-acid region of the gp120 glycoprotein of HIV-1JR–FL. Significantly, this region is upstream from the previously defined CD4-binding domain19. We propose that at least one determinant for mononuclear phagocyte tropism involves target cell interactions with regions of gp120 distinct from the CD4-binding domain.