Chemokine Receptors and HIV-1: An Attractive Pair?

In addition, CD4 can induce conformational changes in the viral glycoproteins, as measured by antibody epi-Department of Microbiology School of Medicine tope changes and gp120 shedding from the virus (reviewed by Sattentau and Moore, 1993), but viral binding and these conformational changes are not sufficient for HIV-1 infection of cells. In nonhuman cells expressing Binding of virus particles to the host cell surface initiates CD4, HIV-1 binds, but virus–host membrane fusion does not occur. This species tropism of HIV-1 suggests that a cascade of events that culminates with the introduction of the viral genetic material into the host cell. For an accessory factor may be required, in addition to CD4, to elicit the correct alterations in Env that lead to mem-enveloped viruses, this cascade begins with the envelope proteins on the virus binding to specific cellular brane fusion. In addition to the species-specific restriction to HIV-1 receptors and is completed following viral glycoprotein– mediated fusion of the viral and target membranes. host range outlined above, there are also restrictions on HIV-1 infection of human cells (reviewed by Miedema Presently, the best model for viral envelope–mediated membrane fusion is that of influenza hemaglutinnin (HA). et al., 1994). Most commonly used laboratory strains of HIV-1 readily infect cultured T cell lines and primary T HA mediates membrane fusion by first binding to its cognate receptor on the host membrane. After endocy-lymphocytes but not primary monocytes or macro-phages. These strains are termed T-tropic. Some pri-tosis, pH-induced conformational changes lead to insertion of a hydrophobic stretch of residues (the so-called mary isolates (viruses not extensively passaged in culture) exhibit a similar replication pattern in T cell lines fusion peptide) of HA into the host membrane. Subsequent to fusion peptide insertion, additional conforma-and macrophages and are also defined as T-tropic. In contrast, most primary HIV-1 isolates grow poorly in tional changes are thought to take place in HA that eventually lead to membrane fusion (reviewed by Carr established T cell lines but will replicate efficiently in primary lymphocytes, as well as in monocytes and and Kim, 1994). The human immunodeficiency virus type 1 envelope macrophages, and are referred to as macrophage-or M-tropic. Importantly, the macrophage-tropic strains (HIV-1 Env) has a number of proposed structural features that are very similar to HA and suggest a common mech-more closely resemble viruses present early and throughout the course of HIV-1 infection. It appears that anism of entry. However, …