Integrase, LEDGF/p75 and HIV replication.
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.
Poeschla
E M
EM
Guggenheim 18, Mayo Clinic College of Medicine, 200 First Street SW, Rochester 55905, USA. emp@mayo.edu
D000595:Amino Acid Sequence; D015316:Genetic Therapy; D005822:Genetic Vectors; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D016662:Virus Integration; D014779:Virus Replication
D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1