BST-2/tetherin-mediated restriction of chikungunya (CHIKV) VLP budding is counteracted by CHIKV non-structural protein 1 (nsP1)

Jones, Philip H.; Maric, Martina; Madison, Marisa N.; Maury, Wendy; Roller, Richard J.; Okeoma, Chioma M.

doi:10.1016/j.virol.2013.01.010

Cited by 94 publications

(124 citation statements)

References 69 publications

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“…In various cells, BST‐2 is induced by type I IFN (IFNα and IFNβ), type II IFN (IFNγ), and type III IFN (IFNλ) 38, 145. Induction of BST‐2 by IFNs occur in a broad range of cell lines, primary cells, and in vivo 4, 8, 28, 38, 45. The effect of IFNs is cell type dependent.…”

Section: Bst‐2 Regulationmentioning

confidence: 99%

The role of BST‐2/Tetherin in host protection and disease manifestation

Mahauad‐Fernandez

Okeoma

2015

Immunity, Inflammation and Disease

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Host cells respond to viral infections by activating immune response genes that are not only involved in inflammation, but may also predispose cells to cancerous transformation. One such gene is BST‐2, a type II transmembrane protein with a unique topology that endows it tethering and signaling potential. Through this ability to tether and signal, BST‐2 regulates host response to viral infection either by inhibiting release of nascent viral particles or in some models inhibiting viral dissemination. However, despite its antiviral functions, BST‐2 is involved in disease manifestation, a function linked to the ability of BST‐2 to promote cell‐to‐cell interaction. Therefore, modulating BST‐2 expression and/or activity has the potential to influence course of disease.

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Section: Bst‐2 Regulationmentioning

confidence: 99%

The role of BST‐2/Tetherin in host protection and disease manifestation

Mahauad‐Fernandez

Okeoma

2015

Immunity, Inflammation and Disease

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“…Tetherin acts on a wide range of enveloped viruses, including members of the Retroviridae, Filoviridae, Arenaviridae, Herpesviridae, Paramyxoviridae, and Togaviridae families (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Viruses have in turn evolved a series of distinct mechanisms to counteract tetherin (1-4, 8, 13, 15-17).…”

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confidence: 99%

Three-Dimensional Structural Characterization of HIV-1 Tethered to Human Cells

Strauss

Hammonds

et al. 2016

J Virol

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Tetherin (BST2, CD317, or HM1.24) is a host cellular restriction factor that prevents the release of enveloped viruses by mechanically linking virions to the plasma membrane. The precise arrangement of tetherin molecules at the plasma membrane site of HIV-1 assembly, budding, and restriction is not well understood. To gain insight into the biophysical mechanism underlying tetherin-mediated restriction of HIV-1, we utilized cryo-electron tomography (cryo-ET) to directly visualize HIV-1 virus-like particles (VLPs) and virions tethered to human cells in three dimensions (3D). Rod-like densities that we refer to as tethers were seen connecting HIV-1 virions to each other and to the plasma membrane. Native immunogold labeling showed tetherin molecules located on HIV-1 VLPs and virions in positions similar to those of the densities observed by cryo-ET. The location of the tethers with respect to the ordered immature Gag lattice or mature conical core was random. However, tethers were not uniformly distributed on the viral membrane but rather formed clusters at sites of contact with the cell or other virions. Chains of tethered HIV-1 virions often were arranged in a linear fashion, primarily as single chains and, to a lesser degree, as branched chains. Distance measurements support the extended tetherin model, in which the coiled-coil ectodomains are oriented perpendicular with respect to the viral and plasma membranes. IMPORTANCETetherin is a cellular factor that restricts HIV-1 release by directly cross-linking the virus to the host cell plasma membrane. We used cryo-electron tomography to visualize HIV-1 tethered to human cells in 3D. We determined that tetherin-restricted HIV-1 virions were physically connected to each other or to the plasma membrane by filamentous tethers that resembled rods ϳ15 nm in length, which is consistent with the extended tetherin model. In addition, we found the position of the tethers to be arbitrary relative to the ordered immature Gag lattice or the mature conical cores. However, when present as multiple copies, the tethers clustered at the interface between virions. Tethered HIV-1 virions were arranged in a linear fashion, with the majority as single chains. This study advances our understanding of tetherin-mediated HIV-1 restriction by defining the spatial arrangement and orientation of tetherin molecules at sites of HIV-1 restriction.

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“…Microscopic scanning of the cell membrane is typically used to visualize virusladen cell membrane ( Fig. 2; Jones et al 2013). Virions can be observed as tethered on the cell membrane individually or linked to each other in groups (Fig.…”

Section: Bst-2-mediated Retention Of Nascent Chikv Particles On Host mentioning

confidence: 99%

“…2b). Aside from endogenous BST-2, exogenously expressed protein is functional and tethers CHIKV virus-like particles on the cell membrane (Jones et al 2013) or restricts CHIKV release into the culture medium (Ooi et al 2015).…”

Section: Bst-2-mediated Retention Of Nascent Chikv Particles On Host mentioning

confidence: 99%