Primitive hematopoietic cells resist HIV-1 infection via p21Waf1/Cip1/Sdi1

Hematopoietic stem cells are resistant to HIV-1 infection. Here, we report a novel mechanism by which the cyclin-dependent kinase inhibitor (CKI) p21 Waf1/Cip1/Sdi1 (p21), a known regulator of stem cell pool size, restricts HIV-1 infection of primitive hematopoietic cells. Modifying p21 expression a...

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Bibliographic Details
Published in:The Journal of clinical investigation 2007-02, Vol.117 (2), p.473-481
Main Authors: Zhang, Jielin, Scadden, David T., Crumpacker, Clyde S.
Format: Article
Language:English
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Summary:Hematopoietic stem cells are resistant to HIV-1 infection. Here, we report a novel mechanism by which the cyclin-dependent kinase inhibitor (CKI) p21 Waf1/Cip1/Sdi1 (p21), a known regulator of stem cell pool size, restricts HIV-1 infection of primitive hematopoietic cells. Modifying p21 expression altered HIV-1 infection prior to changes in cell cycling and was selective for p21 since silencing the related CKIs, p27 Kip1 and p18 INK4C , had no effect on HIV-1. We show that p21 blocked viral infection by complexing with HIV-1 integrase and aborting chromosomal integration. A closely related lentivirus with a distinct integrase, SIVmac-251, and the other cell-intrinsic inhibitors of HIV-1, Trim5α, PML, Murr1, and IFN-α, were unaffected by p21. Therefore, p21 is an endogenous cellular component in stem cells that provides a unique molecular barrier to HIV-1 infection and may explain how these cells remain an uninfected “sanctuary” in HIV disease.
ISSN:0021-9738
DOI:10.1172/JCI28971