CELL BIOLOGY: Outside Inside

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Science  04 May 2007:
Vol. 316, Issue 5825, pp. 662b
DOI: 10.1126/science.316.5825.662b

In macrophages that have been infected by HIV-1, the newly synthesized virions bud into an intracellular compartment, which has been thought to be derived from endosomes because it contains the endosomal membrane protein CD63. However, there currently is some controversy about the site of viral budding because a variety of viral components are directly targeted to the plasma membrane and because virus assembly has clearly been observed on the surface of infected T cells.

Deneka et al. show that, although the budding compartment in macrophages appears at first glance to be intracellular, it is in fact still connected to the cell surface and can be accessed directly from the extracellular milieu. The authors identify several of the membrane proteins—three members of a protein family known as tetraspanins, CD81, CD9, and CD53—that define this unanticipated plasma membrane domain, and confirm that a similar compartment exists in uninfected cells. These membrane-delimited structures were accessible to two membrane-impermeant molecules (horse-radish peroxidase and ruthenium red) added to the external medium and also to antibodies (as long as the cells were kept at 4°C to prevent active uptake). These findings are consistent with recent work by Welsch et al. and by Jouvenet et al. that together support the notion that HIV normally buds from the plasma membrane during productive infection. — SMH

J. Cell Biol. 177, 329 (2007); PLoS Pathog. 3, e36 (2007); PLoS Biol. 4, e435 (2006).

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