Monoubiquitinated Histone H1B Is Required for Antiviral Protection in CD4+T Cells Resistant to HIV-1
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文摘
Linker histone H1B (H1B) coeluted with an antiviral activity during the purification of HIV-1resistance factor (HRF) from supernatants of HRF(+) cells. Western blot analysis of the supernatantusing -H1 and -ubiquitin antibodies detected the same band of roughly 46 kDa; this band was absentfrom the control supernatant. Depletion of histone from biologically active material did not affect itspotential, suggesting that ubiquitinated H1B is not required for the HRF-mediated antiviral protection inHIV-1 susceptible target cells; however, specific silencing of histone H1B via RNAi in HRF(+) cellsreduced the biological activity of cell culture supernatants by 96% and reversed the HIV-1 resistancephenotype of HRF(+) cells. Exposure to HRF induced ubiquitination and secretion of H1B from targetHIV-1 susceptible cells, suggesting that ubiquitinated H1B is a cofactor of HRF, possibly regulating itsexpression and secretion from CD4+T cells induced to resist HIV-1 infection.

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