Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation

Abstract

The genome of the human immunodeficiency virus type 1 (HIV-1) is highly heterogeneous. Some of this genomic variability is reflected in the biologic and serologic differences observed among various strains of HIV-1. To map the viral determinants that correlate with pathogenicity of the virus, recombinant viruses were generated between biologically active molecular clones of HIV-1 strains that show differences in T-cell or macrophage tropism, cytopathogenicity, CD4 antigen modulation, and susceptibility to serum neutralization. The results of these studies indicate that the envelope region contains the major determinants of these viral features. Further studies with sequence exchanges within this region should help identify specific domains that

Human Immunodeficiency Virus Type 1-Associated Cd4 Downmodulation

“…Macrophage-tropic HIV-1 variants from brain failed to modulate cell surface CD4 expression after infection. In this instance, both the capacity for CD4 modulation and macrophage tropism were mapped to the envelope gene (Cheng-Mayer et al, 1990). The failure of CD4 downmodulation in brain may be related to superinfection and accumulation of unintegrated viral DNA in the brains of patients with HIV-1 encephalitis (Pang et al, 1990).…”

Fumagillin suppresses HIV‐1 infection of macrophages through the inhibition of Vpr activity

“…Human embryonic kidney (HEK) 293 cells expressing SV40 large T antigen (293T) were propagated in DMEM medium supplemented with 10% FCS. Human primary monocytes and differentiated macrophages were obtained from peripheral blood mononuclear cells of healthy donors as described [21].…”

Molecular determinants of human immunodeficiency virus type I phenotype variability

“…It is only much later in infection that variability in V3 is observed, giving rise to SI and/or T-cell-tropic viruses. Secondly, the evolution from NSI to SI or macrophage-tropic to T-cell-tropic isolates requires multiple mutations at fixed positions in gp120 rather than random single point-mutations [90,93,100,107,145]. Presuming that evolution of a virus isolate with NSI macrophagetropic phenotype towards SI T-cell-tropic phenotype occurs as a consequence of five or six amino acid substitutions at fixed positions in gp120, the chance of random outgrowth of the virus with this particular genotype is extremely small.…”