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Distribution of ESCRT Machinery at HIV Assembly Sites Reveals Virus Scaffolding of ESCRT Subunits

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Science  07 Feb 2014:
Vol. 343, Issue 6171, pp. 653-656
DOI: 10.1126/science.1247786

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Viral ESCRT

The ESCRT (Endosomal Sorting Complex Required for Transport) protein complex plays a role in budding into multivesicular bodies, cytokinesis, and HIV budding, but the details of how the ESCRTs facilitate viral budding are unclear. Now, using high-resolution light and electron microscopical imaging techniques, Van Engelenburg et al. (p. 653, published online 16 January) dissect the role for ESCRT proteins in HIV budding. The findings suggest that the ESCRT machinery required for the scission of HIV particles from infected cells is located within the core of the virus particle and not, as might have been expected based on previous work, on the cellular side of the membrane scission event involved in viral budding.

Abstract

The human immunodeficiency virus (HIV) hijacks the endosomal sorting complexes required for transport (ESCRT) to mediate virus release from infected cells. The nanoscale organization of ESCRT machinery necessary for mediating viral abscission is unclear. Here, we applied three-dimensional superresolution microscopy and correlative electron microscopy to delineate the organization of ESCRT components at HIV assembly sites. We observed ESCRT subunits localized within the head of budding virions and released particles, with head-localized levels of CHMP2A decreasing relative to Tsg101 and CHMP4B upon virus abscission. Thus, the driving force for HIV release may derive from initial scaffolding of ESCRT subunits within the viral bud interior followed by plasma membrane association and selective remodeling of ESCRT subunits.

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