The Interplay between HIV-1 Gag Binding to the Plasma Membrane and Env Incorporation

• Published in: Viruses Vol. 12; no. 5; p. 548
• Main Authors: Murphy, R Elliot, Saad, Jamil S
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.05.2020; MDPI
• Subjects: Cell Membrane - metabolism; Cell membranes; env Gene Products, Human Immunodeficiency Virus - chemistry; env Gene Products, Human Immunodeficiency Virus - metabolism; envelope; Gag; gag Gene Products, Human Immunodeficiency Virus - chemistry; gag Gene Products, Human Immunodeficiency Virus - metabolism; Glycoproteins; HIV; HIV Antigens - chemistry; HIV Antigens - metabolism; HIV Envelope Protein gp41 - chemistry; HIV Envelope Protein gp41 - metabolism; HIV-1; HIV-1 - metabolism; matrix; membrane; Phosphatidylinositol 4,5-Diphosphate - metabolism; Physiological aspects; Protein Binding; Protein Conformation; retroviruses; Review; Virus Assembly; United States; HIV-1; cytoplasmic tail; envelope; membrane; nuclear magnetic resonance (NMR); Gag; matrix; retroviruses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12050548

Advancement in drug therapies and patient care have drastically improved the mortality rates of HIV-1 infected individuals. Many of these therapies were developed or improved upon by using structure-based techniques, which underscore the importance of understanding essential mechanisms in the replication cycle of HIV-1 at the structural level. One such process which remains poorly understood is the incorporation of the envelope glycoprotein (Env) into budding virus particles. Assembly of HIV particles is initiated by targeting of the Gag polyproteins to the inner leaflet of the plasma membrane (PM), a process mediated by the N-terminally myristoylated matrix (MA) domain and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P ). There is strong evidence that formation of the Gag lattice on the PM is a prerequisite for the incorporation of Env into budding particles. It is also suggested that Env incorporation is mediated by an interaction between its cytoplasmic tail (gp41CT) and the MA domain of Gag. In this review, we highlight the latest developments and current efforts to understand the interplay between gp41CT, MA, and the membrane during assembly. Elucidation of the molecular determinants of Gag-Env-membrane interactions may help in the development of new antiviral therapeutic agents that inhibit particle assembly, Env incorporation and ultimately virus production.