Abstract
Lentiviruses have unusually long envelope (Env) cytoplasmic tails, longer than those of other retroviruses. Whereas the Env ectodomain has received much attention, the gp41 cytoplasmic tail (gp41-CT) is one of the least studied parts of the virus. It displays relatively high conservation compared to the rest of Env. It has been long established that the gp41-CT interacts with the Gag precursor protein to ensure Env incorporation into the virion. The gp41-CT contains distinct motifs and domains that mediate both intensive Env intracellular trafficking and interactions with numerous cellular and viral proteins, optimizing viral infectivity. Although they are not fully understood, a multiplicity of interactions between the gp41-CT and cellular factors have been described over the last decade; these interactions illustrate how Env expression and incorporation into virions is a finely tuned process that has evolved to best exploit the host system with minimized genetic information. This review addresses the structure and topology of the gp41-CT of lentiviruses (mainly HIV and SIV), their domains and believed functions. It also considers the cellular and viral proteins that have been described to interact with the gp41-CT, with a particular focus on subtype-related polymorphisms.
Highlights
envelope glycoprotein (Env) and the entry process The main target cells for the Human Immunodeficiency Virus type 1 (HIV) and Simian Immunodeficiency Virus (SIV) are CD4-expressing cells, namely CD4+ T lymphocytes, dendritic cells (DCs) and macrophages
Initially considered to be inessential for the HIV replication cycle, the gp41-Cytoplasmic tail (CT) has been demonstrated to be a pleiotropic domain: it is required for viral infectivity by ensuring Env incorporation into the virion on one hand, and contributing to enhanced viral replication in target cells through many still incompletely understood interactions on the other
The Env expressed on the surface of infected cells and of virions is one of the most powerful escape mechanisms developed by HIV
Summary
Env and the entry process The main target cells for the Human Immunodeficiency Virus type 1 (HIV) and Simian Immunodeficiency Virus (SIV) are CD4-expressing cells, namely CD4+ T lymphocytes, dendritic cells (DCs) and macrophages. Interactions of the gp41-CT with cellular trafficking regulators (discussed below, ‘Interactions of the gp41-CT with cellular factors and intracellular regulators’) down-modulates Env as soon as it reaches the plasma membrane such that it remains scarce until p55Gag oligomerization is complete or, at least, sufficiently dense in the assembly platforms to ensure efficient viral assembly and release [133] (Figure 3) This mechanism for the regulation of the surface abundance of Env protein may protect infected cells from Envdependent cytopathic effects, from Env-induced Fasmediated apoptosis and/or from Env-specific immune responses [133,134,135,136,137]. It would be useful to assess whether such apparent tolerance identifies interactions that are less vital for viral replication, or whether the virus has acquired other compensatory polymorphisms to override decreased efficiency of that particular interaction
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