Primitive hematopoietic cells resist HIV-1 infection via p21Waf1/Cip1/Sdi1
J. Clin. Invest. Jielin Zhang, et al. 117:473 doi:10.1172/JCI28971 [
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Figure 2p21 restricted HIV-1 replication in cells. (
A) HIV-1 replication in p21 siRNA–treated CD34
+ primary cells. HIV-1 p24 levels were detected at days 4, 7, 10, and 14 after HIV-1 infection. Cells were treated with chemically synthesized p21 siRNA (Si-1, Si-2) or control siRNA (HPRT) or were mock treated. Culture supernatants collected at each time point were analyzed by HIV-1 p24 antigen assay. HIV-1 growth kinetics in mock-treated cells was indistinguishable from that in HPRT siRNA–treated cells. Each point represents the p24 level from 2 separate experiments run in duplicate. Values represent means ± SD (0.2–4.7). (
B) HIV-1 replication in p21 siRNA–treated CMK cells. HIV-1 p24 levels were detected at days 4, 7, 10, and 14 after viral infection. Cells were treated with chemically synthesized p21 siRNA (Si-2), control siRNA, p21 shRNA (p2.3), or vector without shRNA (pU/B) or were mock treated. Each point represents the p24 level from 2 separate experiments run in duplicate. (
C and
D) TPA-induced p21 expression inhibited HIV-1 replication in CMK cells. Cells were treated with TPA for 1 day (T1), 2 days, or 3 days or were mock treated before HIV-1 infection. (
C) p21 mRNA levels examined at day 12 compared with mock-treated control. (
D) HIV-1 p24 levels determined at days 1, 7, 10, and 12. Each bar represents the p24 level from 2 separate experiments run in duplicate. Values represent means ± SD (0.3–2.6). (
E) HIV-1 p24 expression from transduced p21
–/– and p21
+/+ fibroblasts. The p24 level in culture supernatant was determined at days 3 and 7 after transduction with a single cycle of HIV-1
NLX.Luc(R–) infection. Results are from a representative experiment, and samples run in triplicate. Values represent means ± SD (0.07–0.3).