Virology

Location, Location, Location

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Science  05 Jul 2013:
Vol. 341, Issue 6141, pp. 11
DOI: 10.1126/science.341.6141.11-b
CREDIT: O. S. MAGAÑA-LOAIZA ET AL., APPLIED PHYSICS LETTERS 102, 231104 (10 JUNE 2013) © 2013 AIP PUBLISHING LLC

The ability of HIV to reside in a latent form in T cells is a major hurdle to finding a cure. With no widely protective vaccine on the horizon, there is growing interest in understanding how to convert latent HIV into a replication active state, which would allow therapies that target infected cells to eliminate them. Mechanisms that contribute to HIV latency, however, are poorly understood. Using a combination of immuno-3D fluorescent in situ hybridization and chromatin immunoprecipitation, Lusic et al. find that location matters for latency. In T cell lines and in a model of primary T cells chronically infected with HIV, silenced but not active provirus was located close to nuclear bodies, as measured by their association with promyelocytic leukemia protein (PML), a marker of these structures. The blockade or silencing of PML led to the activation of viral transcription. This was associated with a loss of binding to the methyltransferase G9a and a loss of epigenetic silencing marks from the proviral DNA. Actin-mediated movement away from nuclear bodies was required for transcriptional activation of the virus. Whether modulation of these pathways may be used therapeutically to reactivate and eradicate infected cells remains to be determined.

Cell Host Microbe 13, 665 (2013).

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