Single-molecule imaging of HIV-1 envelope glycoprotein dynamics and Gag lattice association exposes determinants responsible for virus incorporation.
Nairi PezeshkianNicholas S GrovesSchuyler B van EngelenburgPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
The HIV-1 envelope glycoprotein (Env) is sparsely incorporated onto assembling virus particles on the host cell plasma membrane in order for the virus to balance infectivity and evade the immune response. Env becomes trapped in a nascent particle on encounter with the polymeric viral protein Gag, which forms a dense protein lattice on the inner leaflet of the plasma membrane. While Env incorporation efficiency is readily measured biochemically from released particles, very little is known about the spatiotemporal dynamics of Env trapping events. Herein, we demonstrate, via high-resolution single-molecule tracking, that retention of Env trimers within single virus assembly sites requires the Env cytoplasmic tail (CT) and the L12 residue in the matrix (MA) domain of Gag but does not require curvature of the viral lattice. We further demonstrate that Env trimers are confined to subviral regions of a budding Gag lattice, supporting a model where direct interactions and/or steric corralling between the Env-CT and a lattice of MA trimers promote Env trapping and infectious HIV-1 assembly.
Keyphrases
- single molecule
- antiretroviral therapy
- high resolution
- hiv positive
- hiv infected
- human immunodeficiency virus
- hepatitis c virus
- hiv testing
- hiv aids
- sars cov
- atomic force microscopy
- heart failure
- men who have sex with men
- mitral valve
- magnetic resonance
- single cell
- living cells
- magnetic resonance imaging
- contrast enhanced
- stem cells
- amino acid
- positron emission tomography
- bone marrow
- toll like receptor
- photodynamic therapy
- left ventricular
- dual energy
- atrial fibrillation
- binding protein
- cancer therapy