Cell-to-Cell Transfer of HIV-1 via Virological Synapses Leads to Endosomal Virion Maturation that Activates Viral Membrane Fusion

Dale, Benjamin M.; McNerney, Gregory P.; Thompson, Deanna L.; Hübner, Wolfgang; Reyes, Kevin de los; Chuang, Frank Y.S.; Huser, Thomas; Chen, Benjamin

doi:10.1016/j.chom.2011.10.015

Cited by 123 publications

(170 citation statements)

References 34 publications

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“…In an interesting twist, Melikyan and co-workers (62) found that hemifusion occurred at the plasma membrane but that pore expansion occurred following endocytosis in the endosome. Although the endocytic pathway was revealed by observation on the micrometer scale (62,63), it was not supported by examination on the nanoscale in primary lymphocytes (64). Inhibitors of dynaminand clathrin-dependent endocytosis (62,65) have been invoked to argue for HIV entry via endocytosis, but such inhibitors have multifaceted effects on cellular processes, including cell-cell fusion (66).…”

Section: Microscale Determination Of the Hiv Fusion Cascadementioning

confidence: 99%

HIV Entry and Envelope Glycoprotein-mediated Fusion

Blumenthal

Durell

Viard

2012

Journal of Biological Chemistry

186

203

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HIV entry involves binding of the trimeric viral envelope glycoprotein (Env) gp120/gp41 to cell surface receptors, which triggers conformational changes in Env that drive the membrane fusion reaction. The conformational landscape that the lipids and Env navigate en route to fusion has been examined by biophysical measurements on the microscale, whereas electron tomography, x-rays, and NMR have provided insights into the process on the nanoscale and atomic scale. However, the coupling between the lipid and protein pathways that give rise to fusion has not been resolved. Here, we discuss the known and unknown about the overall HIV Env-mediated fusion process. The Virus and Its TargetHIV virions exist as roughly spherical nanoparticles ϳ100 nm in diameter and are coated by the viral envelope membrane (1). The viral membrane is a lipid bilayer ϳ4 nm thick, interspersed with membrane-embedded glycoproteins. The HIV matrix protein Gag Pr55 drives viral assembly by recruiting all the building blocks, which include both viral and cellular components required for the formation of a fully infectious virion (2). A typical HIV viral membrane contains ϳ300,000 lipids, with a rather unique distribution of lipids compared with the lipid composition of cells from which it is derived (3,4). In addition to the virally encoded envelope glycoprotein gp120/ gp41, the HIV membrane also incorporates a plethora of cell membrane proteins in the process of assembly and budding (5). The HIV envelope proteins are expressed in the endoplasmic reticulum as a precursor protein, gp160, which transits the Golgi apparatus, where glycosylation is completed (6, 7). The precursor is cleaved in the trans-Golgi by the cellular protease furin into two proteins, gp120 and gp41 (8). These proteins are present on the cell surface as the envelope complex, a mushroomshaped trimer of heterodimers of gp120 and gp41, incorporated into the viral envelope through the transmembrane region of gp41 as virus particles bud from the cell surface (9).The number of gp120/gp41 trimers per virion ranges between 10 and 100 depending on the isolate (10). HIV gp120 is ϳ50% carbohydrate and is one of the most glycosylated proteins known (11). The number of accessory HIV membrane proteins has, in general, not been determined, with the exception of HLA class II in HIV-1 MN derived from H9 cells, which has ϳ50 native HLA class II complexes (12). The lipids and proteins are glycoconjugated, providing an additional shield for HIV against immune and environmental challenges. The viral genome is thus comfortably ensconced in a wrapper of lipid and protein covered by carbohydrate. However, mannose-type carbohydrates on HIV are recognized by DC-SIGN (dendritic cellspecific intercellular adhesion molecule-3-grabbing non-integrin), which is a C-type lectin receptor present on dendritic cells (13). The dendritic cells internalize HIV-DC-SIGN complexes and migrate to the lymph nodes, where they interact with T cells. The HIV-DC-SIGN complexes are then recycled to the cell periphery, and ...

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Section: Microscale Determination Of the Hiv Fusion Cascadementioning

confidence: 99%

HIV Entry and Envelope Glycoprotein-mediated Fusion

Blumenthal

Durell

Viard

2012

Journal of Biological Chemistry

186

203

View full text Add to dashboard Cite

show abstract

“…In addition, HIV-1 particles transmitted through virological synapses could, at least temporarily, be attached to both cells across the contact area (88). The fact that cell-to-cell transmission does not normally lead to cell fusion suggests negative regulation of this entry pathway, perhaps through delayed virus maturation (89) or through host factors interfering with the fusion process (90,91). If complete HIV-1 fusion at the cell surface relies on actin, what drives pore dilation in endosomes following CD4-and coreceptor-mediated uptake?…”

Section: Hiv-cell and Hiv-mediated Cell-cell Fusion Are Differentlymentioning

confidence: 99%

Distinct Requirements for HIV-Cell Fusion and HIV-mediated Cell-Cell Fusion

Kondo

Marin

Kim

et al. 2015

Journal of Biological Chemistry

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“…De même, on ne connaît pas les mécanismes précis d'entrée du virus HTLV-1 dans la cellule cible lors de la transmission synaptique, ou lors du transfert de biofilm. Y a-t-il fusion à la membrane, ou, comme dans le cas du VIH-1, endocytose des particules virales et fusion dans les endosomes [45] ? Enfin, la nécessité d'un contact étroit entre une cellule infectée et sa cible suggère que le succès de l'infection pourrait aussi dépendre de signaux complémentaires induits par l'engagement de protéines cellulaires au moment du contact.…”

Section: Les Conduits : Réseaux Facilitant La Transmissionunclassified