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Poeschla EM 《Cellular and molecular life sciences : CMLS》2008,65(9):1403-1424
HIV integrates a DNA copy of its genome into a host cell chromosome in each replication cycle. The essential DNA cleaving
and joining chemistry of integration is known, but there is less understanding of the process as it occurs in a cell, where
two complex and dynamic macromolecular entities are joined: the viral pre-integration complex and chromatin. Among implicated
cellular factors, much recent attention has coalesced around LEDGF/p75, a nuclear protein that may act as a chromatin docking
factor or receptor for lentiviral pre-integration complexes. LEDGF/p75 tethers HIV integrase to chromatin, protects it from
degradation, and strongly influences the genome-wide pattern of HIV integration. Depleting the protein from cells and/or over-expressing
its integrase-binding domain blocks viral replication. Current goals are to establish the underlying mechanisms and to determine
whether this knowledge can be exploited for antiviral therapy or for targeting lentiviral vector integration in human gene
therapy.
Received 25 November 2007; received after revision 7 January 2008; accepted 10 January 2008 相似文献
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