Maturation-Dependent HIV-1 Surface Protein Redistribution Revealed by Fluorescence Nanoscopy

  title={Maturation-Dependent HIV-1 Surface Protein Redistribution Revealed by Fluorescence Nanoscopy},
  author={Jakub Chojnacki and Thorsten M. Staudt and B{\"a}rbel Glass and Pit Bingen and Johann Engelhardt and Maria Anders and Jale Schneider and Barbara M{\"u}ller and Stefan W. Hell and Hans‐Georg Kr{\"a}usslich},
  pages={524 - 528}
Switching on HIV Newly assembled human immunodeficiency virus (HIV) virions bud from the host cell as immature particles. Proteolysis of the Gag protein, which forms a structural lattice below the viral membrane, leads to the formation of mature infectious HIV. Fusion of mature HIV virions with a target cell is mediated by viral envelope (Env) proteins that occur in trimeric “spikes” on the surface of the virion. Chojnacki et al. (p. 524) used subdiffraction microscopy to show that the spikes… 

Single molecule fate of HIV-1 envelope reveals late-stage viral lattice incorporation

It is shown that Env distribution is biased toward the necks of cell-associated particles during assembly, and it is postulated that this neck-biased distribution is regulated by vesicular retention and steric complementarity of Env during independent Gag lattice formation.

Envelope glycoprotein mobility on HIV-1 particles depends on the virus maturation state

Molecular dynamics of Env on the surface of individual HIV-1 particles are determined using scanning fluorescence correlation spectroscopy on a super-resolution STED microscope to find that Env undergoes a maturation-induced increase in mobility, highlighting diffusion as one cause for Env clustering.

Maturation of the matrix and viral membrane of HIV-1

The data suggest that proteolytic maturation of HIV-1 not only assembles the viral capsid surrounding the genome but also repurposes the membrane-bound MA lattice for an entry or postentry function and results in the partial removal of up to 2500 lipids from the viral membrane.

Single-molecule imaging of HIV-1 envelope glycoprotein dynamics and Gag lattice association exposes determinants responsible for virus incorporation

It is demonstrated, via high-resolution single-molecule tracking, that retention of Env trimers within single virus assembly sites requires the Env cytoplasmic tail and the L12 residue in the matrix (MA) domain of Gag but does not require curvature of the viral lattice.

HIV-1 Maturation

The current state of knowledge regarding HIV-1 maturation is reviewed, including structural and mechanistic aspects as well as the consequences of its inhibition, including drugs targeting the viral protease.

Super-Resolution Microscopy Reveals Specific Recruitment of HIV-1 Envelope Proteins to Viral Assembly Sites Dependent on the Envelope C-Terminal Tail

Results show that Env is recruited to HIV-1 assembly sites in a CT-dependent manner, while Env(ΔCT) appears to be randomly incorporated, which could facilitate viral spread in vivo.

Clustering and Mobility of HIV-1 Env at Viral Assembly Sites Predict Its Propensity To Induce Cell-Cell Fusion

While Env trapping by Gag secures Env incorporation into viral particles, Env clustering and its sequestration at assembly sites likely also leads to the repression of its fusion function, and thus, by preventing the formation of syncytia, Gag helps to secure efficient transfer of viral particles to target cells.

Virus Particle Release from Glycosphingolipid-Enriched Microdomains Is Essential for Dendritic Cell-Mediated Capture and Transfer of HIV-1 and Henipavirus

The results suggest that GSL incorporation into virions is critical for the interaction of diverse enveloped RNA viruses with DCs and that the GSL-CD169 recognition nexus might be a conserved viral mechanism of parasitization of DC functions for systemic virus dissemination.

Optimized Microbial Recombinant Production of HIV-1 Anti-Envelope Antibody Fragments with Applications to Single Particle Tracking of Virus Assembly

A set of protocols to recombinantly produce, purify and apply various fluorescent probes in vitro for the fluorescent labeling and study of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein during HIV viral assembly is established.



Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography

Cryo-electron tomography and subtomogram averaging are used to resolve the structure of the Gag lattice in a panel of viruses containing point mutations abolishing cleavage at individual or multiple Gag cleavage sites and describe the structural intermediates correlating with the ordered processing events that occur during the HIV-1 maturation process.

Coupling of Human Immunodeficiency Virus Type 1 Fusion to Virion Maturation: a Novel Role of the gp41 Cytoplasmic Tail

A mechanism by which binding of the gp41 cytoplasmic tail to Gag within immature HIV-1 particles inhibits Env conformational changes on the surface of the virion that are required for membrane fusion is suggested.

The long cytoplasmic tail of gp41 is required in a cell type-dependent manner for HIV-1 envelope glycoprotein incorporation into virions.

  • T. MurakamiE. Freed
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
It is found that in the majority of T cell lines, and in primary cell types that serve as natural targets for HIV-1 infection in vivo, the gp41 cytoplasmic tail is essential for efficient Env incorporation into virions.

A stiffness switch in human immunodeficiency virus.

HIV regulates its mechanical properties at different stages of its life cycle and that this regulation may be important for efficient infectivity, establishing the groundwork for mechanistic studies of how retroviral particles can regulate their mechanical properties to affect biological function.

Regulation of Human Immunodeficiency Virus Type 1 Env-Mediated Membrane Fusion by Viral Protease Activity

Examination of the ability of wild-type HIV-1 Env and a mutant lacking the gp41 cytoplasmic tail to induce fusion in the context of an active (PR+) or inactive (PR−) viral PR suggests that interactions between unprocessed Gag and thegp41 cy toplasmo tail suppress fusion.

Electron Tomography of the Contact between T Cells and SIV/HIV-1: Implications for Viral Entry

The three-dimensional architectures of purified SIV virions in isolation and in contact with CD4+ target cells are determined and the molecular composition and structure of the entry claw may facilitate the identification of improved drugs for the inhibition of HIV-1 entry.

HIV-1–cellular interactions analyzed by single virus tracing

From the trajectories of freely diffusing VLPs in solution, it is established that the particle preparation was homogeneous and the particles had a hydrodynamic radius of 86 ± 5 nm, consistent with the size of single HI viruses.

Distribution and three-dimensional structure of AIDS virus envelope spikes

Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions.

A sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytes

A simple, rapid assay allowing the detection of HIV-1 virion fusion to biologically relevant target cells, including primary CD4+ T lymphocytes is developed.