Understanding the process of envelope glycoprotein incorporation into virions in simian and feline immunodeficiency viruses

Abstract

The lentiviral envelope glycoproteins (Env) mediate virus entry by interacting with specific receptors present at the cell surface, thereby determining viral tropism and pathogenesis. Therefore, Env incorporation into the virions formed by assembly of the viral Gag polyprotein at the plasma membrane of the infected cells is a key step in the replication cycle of lentiviruses. Besides being useful models of human immunodeficiency virus (HIV) infections in humans and valuable tools for developing AIDS therapies and vaccines, simian and feline immunodeficiency viruses (SIV and FIV, respectively) are relevant animal retroviruses; the study of which provides important information on how lentiviral replication strategies have evolved. In this review, we discuss the molecular mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into viral particles.

Figure 1

Domain organization of SIV_SMM-PBj gp41. The major gp41 structural regions are indicated: ectodomain, membrane-spanning domain (MSD) and cytoplasmic tail. The functional motifs within the ectodomain are depicted: the fusion peptide (FP) and the two heptad-repeats (HR1 and HR2). In the cytoplasmic domain, the two potential amphipathic α-helices are shown: lentiviral lytic peptides 2 and 1 (LLP-2 and LLP-1, respectively). Numbers correspond to the amino acid positions in the Env protein.

Figure 2

The amino terminal region of the matrix (MA) domain of SIV_SMM-PBj Gag. (Top) The domains of the SIV Gag polyprotein are depicted: matrix (MA, 135 amino acids), capsid (CA, 230 amino acids), nucleocapsid (NC, 52 amino acids), p6 (59 amino acids) and the spacer peptides SP1 (17 amino acids) and SP2 (14 amino acids). (Bottom) The amino acid sequence of the first 46 residues of the SIV MA is shown, indicating the α-helices 1 and 2, the β-turn, and the membrane-binding competent motifs: the myristic moiety that modifies the glycine at position 2 (arrow), the valine 7 and leucine 8 (underlined), and the polybasic region (amino acids 26–32, highlighted in red).

Figure 3

The crystal structure of the SIV MA (PDB 1ED1). A stereo view of the monomeric form of the protein (residues 6 to 119). The α-helices H1 to H7 are indicated as well as the amino and carboxyl termini of the molecule.

Figure 4

Schematic diagram of the feline immunodeficiency virus (FIV) Env glycoprotein. (Top) The leader peptide and the surface (SU) and transmembrance (TM) subunits are shown. The three major regions that constitute the TM are indicated: ectodomain (red box), membrane-spanning domain (grey box) and the cytoplasmic tail (light-blue box). Amino acid numbering corresponds to the Env protein of the Petaluma isolate. (Bottom) Amino acid sequences of the membrane anchor and the cytoplasmic domain of FIV Env. The four highly conserved cysteines as well as the tyrosine-based endocytosis motif within the cytoplasmic tail are highlighted below the sequence.