Monoubiquitinated histone H1B is required for antiviral protection in CD4(+)T cells resistant to HIV-1.
Linker histone H1B (H1B) coeluted with an antiviral activity during the purification of HIV-1 resistance factor (HRF) from supernatants of HRF(+) cells. Western blot analysis of the supernatant using alpha-H1 and alpha-ubiquitin antibodies detected the same band of roughly 46 kDa; this band was absent from the control supernatant. Depletion of histone from biologically active material did not affect its potential, suggesting that ubiquitinated H1B is not required for the HRF-mediated antiviral protection in HIV-1 susceptible target cells; however, specific silencing of histone H1B via RNAi in HRF(+) cells reduced the biological activity of cell culture supernatants by 96% and reversed the HIV-1 resistance phenotype of HRF(+) cells. Exposure to HRF induced ubiquitination and secretion of H1B from target HIV-1 susceptible cells, suggesting that ubiquitinated H1B is a cofactor of HRF, possibly regulating its expression and secretion from CD4(+)T cells induced to resist HIV-1 infection.
Lesner
Adam
A
Molecular Virology Division, St. Luke's/Roosevelt Hospital Center, Columbia University, New York, New York 10019, USA.
Kartvelishvili
Alex
A
Lesniak
Jakob
J
Nikolov
Dimitar
D
Kartvelishvili
Magdalena
M
Trillo-Pazos
Gusta
G
Zablotna
Ewa
E
Simm
Malgorzata
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006657:Histones / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D006657:Histones; D025801:Ubiquitin