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A novel family of host cell factors that control hiv production by targeting rev.

Vortrag: 34th Annual Meeting on Retroviruses in CSHL, 17th May 2009, CSHL, NY, USA. (2009)
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HIV-1 Rev is a key inducer of virus replication. Rev facilitates different post-transcriptional events required for the production of viral proteins and RNA genomes. We previously identified a novel Rev-interacting protein termed Risp that is capable of modulating the expression of Revdependent reporter genes. In this report we investigated production of Risp-proteins in lysates of human astrocytes, which are known to restrict HIV production and to suppress Rev activity. We identified several Rispproteins of different sizes. Three of these proteins were shown to interact with Rev in an affinity chromatography–based assay for capture of Revinteractors. Rev shows abnormal cytoplasmic accumulation in astrocytes and we found that Risp proteins also localize to the cytoplasm. RNAi knock-down of Risp expression increased nuclear levels of Rev, suggesting that Risp proteins retain Rev in the cytoplasm. Overexpression and RNAi analyses in a persistently HIV-infected astrocyte model showed negative regulation of HIV replication by Rispproteins. Altogether, we demonstrate that proteins of the Risp-family can interact with Rev and strongly inhibit HIV-1 replication, identifying the first host-cell factors that control HIV production by targeting Rev.
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Publikationstyp Sonstiges: Vortrag
Konferenztitel 34th Annual Meeting on Retroviruses in CSHL
Konferzenzdatum 17th May 2009
Konferenzort CSHL, NY, USA