Maturation and assembly of retroviral glycoproteins.

Abstract

Retroviruses infect cells after binding to a diverse set of specific cell surface receptors via their envelope glycoproteins (Env) (reviewed in (Weiss 1993). Retroviralenv genes are translated into a precursor protein that enters the secretory pathway of the host cell. During the process of being transported to the plasma membrane, the site at which the glycoproteins become incorporated into virions, the precursor undergoes maturation to a bipartite complex composed of the N-terminal, external surface subunit (SU), and a membrane-spanning Cterminal protein (TM). The receptor specificity of the complex is determined in large part, if not exclusively, by the SU domain, which retains receptor binding activity outside of the complex with T M (Delarco and Todaro 1976; Lasky et al. 1987). The diversity of receptor specificities within some groups of retroviruses has facilitated the identification of regions of the SU proteins that contribute to receptor binding. The heterogeneity of SU proteins that is apparent fromenv sequences of different retroviruses suggests that the structural details of Env-receptor interactions may vary among these viruses. In addition, the sequences or domains that have been implicated in receptor binding differ in their positions within SU. The gp70 of the murine leukemia viruses (MuLVs) appears to be organized into N-terminal and C-terminal structural domains with the receptor-binding determinants in the N-terminal region (Battini et al. 1992; Heard and Danos 1991; Morgan et al. 1993; Ott and Rein 1992), while receptor specificity of avian sarcoma and leukemia virus (ASLV) Env is dependent on sequence in the middle third of S U (Bova et al. 1986, 1988; Dorner and Coffin 1986; Dorner et al. 1985). Receptor binding by gp120 of human immunodeficiency virus (HIV-1) involves a major determinant in the C-terminal third of the protein together with discrete segments from other regions of the protein (Cordonnier et al. 1989; Dowbenko et al. 1988; Lasky et al. 1987; Olshevsky et al. 1990; Pollard et al. 1992). Whether these differences extend to the structures of the SU proteins or only indicate variety in the interaction of a relatively conserved structure with different receptors is unclear.