The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated.

Abstract

The envelope proteins of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) were found to be modified by fatty acylation of the transmembrane protein subunit gp4l. The precursor gpl60 was also palmitoylated prior to its cleavage into the gpl20 and gp4l subunits. The palmitic acid label was sensitive to treatment with hydroxylamine or 2-mercaptoethanol, indicating that the linkage is through a thioester bond. Treatment with cycloheximide did not prevent the incorporation of [3H]palmitic acid into the HIV envelope protein, indicating that palmitoylation is a posttranslation modification. In contrast to other glycoproteins, which are palmitoylated at cysteine residues within or close to the membrane-spanning hydrophobic domain, the palmitoylation of the HIV-1 envelope proteins occurs on two cysteine residues, Cys-764 and Cys-837, which are 59 and 132 amino acids, respectively, from the proposed membrane-spanning domain of gp4l. Sequence comparison revealed that one of these residues (Cys-764) is conserved in the cytoplasmic domains of almost all HIV-1 isolates and is located very close to an amphipathic region which has been postulated to bind to the plasma membrane.

Palmitoylation of the HIV-1 envelope glycoprotein is critical for viral infectivity

“…gp160 is proteolytically processed into the receptor-binding domain, gp120 (green), and the transmembrane domain gp41-composed of an ectodomain (red), transmembrane helix (TM, black), and cytoplasmic domain (blue). The cytoplasmic domain contains two palmitoylated cysteine residues at positions 764 and 837 (22). The location of the gp160 mAb (Chessie-8) recognition sequence (PDR-PEG) is indicated (27).…”

“…Removal of all three palmitoylation sites on HA recently was shown to dramatically decrease HA incorporation into virions (24). For HIV-1 Env, removal of the palmitoylation sites was shown to have no effect on envelope expression or cellular trafficking (22). It is unknown, however, if palmitoylation of gp160 plays a role in the virus life cycle.…”

The Effects of HIV-1 Nef on CD4 Surface Expression and Viral Infectivity in Lymphoid Cells Are Independent of Rafts

“…The viral envelope glycoprotein is palmitoylated, potentially promoting its localization within rafts (56,72). The Gag precursor p55 is also preferentially found in rafts, or in raft-like detergent-resistant complexes, where oligomerization and maturation may be facilitated (51)(52)(53)(54)(55).…”

“…CD4 palmitoylation occurs on two membrane proximal residues (49,71) and also requires a short cluster of positively charged residues within the cytoplasmic tail (50). HIV-1 Env glycoproteins are palmitoylated on two intracellular cysteines (56,72). Mutating these residues did not affect cell fusion activity or surface expression of HIV-1 Env, but abrogated raft association, virion incorporation, and viral infectivity.…”

Do lipid rafts mediate virus assembly and pseudotyping?

“…Retroviral Gag proteins are myristoylated and the glycoproteins of retroviruses, filoviruses and influenza viruses may be palmitoylated (Ito et al, 2001;Schmidt, 1982Schmidt, , 1984Yang et al, 1995). There is increasing evidence that a number of virus proteins, with or without modifications, are raft associated and that assembly and budding of virions may take place through rafts.…”