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A targeting Fusion Protein XE-TNFαm2 Stimulates Latent HIV to Re-propagate and then Kills the Host Cells with un-mature HIV |
1.Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences/Peking Union Medical College,Beijing 100005,China
2.Institute of Laboratory Animal Sciences,CAMS/PUMC, Beijing 100021,China
3.Institute of Blood Transfusion, CAMS, Chengdu 610081,China |
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Abstract Engineered targeting fusion protein XE-TNFαm2 was prepared.In which,XE is the second excellular domain of CXCR4,a co-receptor of HIV/SIV. TNFαm2 is a mutation protein of TNFα.Its side effect was reduced 18 fold.It has been used in clinic for cancer therapy.In this study, Jurkat H2/9855, a standard cell line was donated toward by AIDS Reagent Program, NIH ,USA.In which, a deleted HIV mutant was inserted into chromosome of Jurkat cells to be 5’LTR-Tat-GFP-3’LTR. XE-TNFαm2 with different doses were added into 1x105/ml Jurkat H2/9855 cell suspensions respectively. After 24hrs,48 hrs and 72 hrs,the GFP in samples were determined by flow cytometry. The results showed that the increase of GFP expression level is along with the extended time of treatment with XE-TNFαm2,and it is depended on the dosage of XE-TNFαm2. This result indicated that XE-TNFαm2 is able to stimulate latent HIV to re-propagate in Jurkat H2/9855 cells.Thus,the host cell were became to be novel infected cells. On the other aspect, our previous study indicated that one of XE-TNFαm2 functions is to kill the cells infected by HIV/SIV. Accordingly, when the novel re-propagating HIVs start to pullulate, their gp120 must be appeared on the surface of host cells. Then,gp120 must be bound by XE in XE-TNFαm2, and latter’s killing signal must be transduced into cells.In that case, these host cells must be killed by XE-TNFαm2. Thus, the death of host cells leads to stop the propagation of un-maturated HIVs. Then, such kind of HIV without infection ability must be eliminated together with died host cells before that the re-propagated HIVs maturated to break host cells and to release out from cells.
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Received: 01 February 2010
Published: 26 February 2010
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[1] Anne Brelot, Nikolaus Heveker, Monica Montes,et al.Identification of residues of CXCR4 critical for human immunodeficiency virus coreceptor and chemokine receptor activities.J Biologlcal Chemistry,2000,275(31):2373623744.
[2] Donald J Chabot, Pengfel Zhang.Mutagenesis of CXCR4 identifies important domains for human immunodeficiency virus Type 1 X4 isolate envelopemediated membrane fusion and virus entry and reveals cryptic coreceptor activity for R5 isolates. J Virology,1999,73(8):65986609.
[3] Nakamura S, Kato A, Masegi T,et al. A novel recombinant tumor necrosis factoralpha mutant with increased antitumor activity and lower toxicity. Int J Cancer,1991,48(5):744748.
[4] Weinberger L S, Burnett J C, Toettcher J E,et al.Stochastic gene expression in a lentiviral positivefeedback loop: HIV1 Tat fluctuations drive phenotypic diversity.Cell,2005,122:169182.
[5] Qi X, Koya Y, Saitoh T,et al.Efficient induction of HIV1 replication in latently infected cells through contact with CD4+ T cells: involvement of NFkappaB activation. Virology,2007,361:325334.
[6] Duh E J, Maury W J, Folks T M,et al.Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NFkappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A,1989,86:59745978.
[7] Brooks D G, Arlen P A, Gao L, et al.Identification of T cellsignaling pathways that stimulate latent HIV in primary cells. Proc Natl Acad Sci U S A,2003,100:1295512960.
[8] 路金芝,陈伟京,杨晶,等.靶向融合蛋白XETNFαm2 导致受HIV/SIV感染细胞的凋亡 中国生物工程杂志, 2009,29(3):913.Lu J Z,Chen W J,Yang J,et al.China Biotechology,2009,29(3):913. |
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