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• W2045201384 abstract "The endless battle between mammalian host cells and microbes has evolved mechanisms to shut down the expression of exogenous transcriptional units integrated into the genome with the goal of limiting their spreading. Recently, we observed that deprivation of essential amino acids leads to a selective, reversible upregulation of expression of exogenous transgenes, either carried by integrated plasmids or retroviral vectors, but not of their endogenous counterparts. This effect was dependent on epigenetic modifications and was mediated by the downregulation of the class II histone deacetylase-4 (HDAC4). Indeed, HDAC4 expression inversely correlated with that of the transgene and its inhibition or downregulation enhanced transgene expression. Could this be true also for naturally integrated proviruses? We investigated this question in the case of HIV-1, the etiological agent of AIDS and we observed that both amino acid starvation and HDAC4 inhibition triggered HIV-1 reactivation in chronically infected ACH-2 T lymphocytic cells (HDAC4+), but not in similarly infected U1 promonocytic cells (HDAC4-negative). Thus, an HDAC4-dependent pathway may contribute to unleash virus expression by latently infected cells, which represent nowadays a major obstacle to HIV eradication. We discuss here the implications and open questions of these novel findings, as well as their serendipitous prelude." @default.
• W2045201384 created "2016-06-24" @default.
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• W2045201384 date "2012-09-01" @default.
• W2045201384 modified "2023-10-14" @default.
• W2045201384 title "Passport control for foreign integrated DNAs" @default.
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• W2045201384 doi "https://doi.org/10.4161/mge.22610" @default.
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