5 A Protein Related to the LDL Receptor Is a Cellular Receptor Specific for Subgroup A Avian Leukosis and Sarcoma Viruses

Abstract

Retrovirus entry into cells requires the binding of viral envelope (Env) glycoproteins to specific host cell-surface receptors. Such interactions presumably activate the fusogenic potential of Env, leading to fusion of virus and cell membranes and entry of viral nucleoprotein core particles into the target cell cytoplasm. Despite the critical importance of these steps in virus infection, the early events in the retrovirus replication cycle are not well understood.

The Env proteins of retroviruses comprise two subunits, surface (SU) and transmembrane (TM) proteins, that are arranged as oligomeric complexes on the viral surface lipid bilayer (Einfeld and Hunter 1988; Pinter et al. 1989; Weiss et al. 1990). The receptor-binding determinants on the virus are commonly found in the SU Env protein (for review, see Weiss 1992). The TM viral Env protein contains the transmembrane and cytoplasmic tail domains that anchor Env at the virus surface, as well as a hydrophobic domain, designated the fusion peptide, that is required for membrane fusion (White 1990).

Since retrovirus envelope proteins resemble the HA1 and HA2 hemagglutinin proteins of influenza virus, it has been suggested that there may be a similar mechanism of membrane fusion mediated by these different viral surface proteins (White 1990). The pH-dependent entry of influenza virus into cells is relatively well understood. After influenza virus binds cell-surface sialic acid, it is taken up by receptor-mediated endocytosis and transported to late endosomes. The low pH within late endosomes drives structural changes in HA1 and HA2, leading to exposure of the hydrophobic fusion...