JCI：成功从猴子身上复制抗艾滋病毒基因

owl monkey

瑞士日内瓦大学研究人员8日在其发表的一项研究成果中宣布，他们成功复制了一种南美猴子体内具有抗艾滋病毒功能的基因，这将可能为一种新型艾滋病疗法的诞生铺平道路。

当天发表在《临床调查学报》电子版上的这项研究成果称，研究人员成功复制了猫头鹰猴（owl monkey）体内抗艾滋病毒基因后，将其植入与人类免疫学特征相同的转基因老鼠体内，发现该基因仍具有与原基因相同的抗艾滋病毒的能力。

该研究小组负责人卢班教授表示，这种基因的成功复制表明它将有可能作为现有抗艾滋病毒药物的替代手段，用作艾滋病基因治疗。

生活在南美洲的猫头鹰猴体内这种有抗艾滋病功能的基因，是卢班教授2004年带领美国哥伦比亚大学的一组科学家发现的。（生物谷Bioon.com）

生物谷推荐原始出处：

J. Clin. Invest. doi:10.1172/JCI39354.

Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components

Martha R. Neagu1,2,3, Patrick Ziegler2, Thomas Pertel2,3, Caterina Strambio-De-Castillia2, Christian Grütter4, Gladys Martinetti5, Luca Mazzucchelli6, Markus Grütter4, Markus G. Manz2,7 and Jeremy Luban1,2,3,8

1Department of Microbiology and Columbia University, New York, New York, USA.
2Institute for Research in Biomedicine, Bellinzona, Switzerland.
3Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
4Department of Biochemistry, University of Zurich, Zurich, Switzerland.
5Institute of Microbiology, Bellinzona, Switzerland.
6Institute for Pathology, Locarno, Switzerland.
7Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
8Department of Medicine, Columbia University, New York, New York, USA.

New World monkeys of the genus Aotus synthesize a fusion protein (AoT5Cyp) containing tripartite motif-containing 5 (TRIM5) and cyclophilin A (CypA) that potently blocks HIV-1 infection. We attempted to generate a human HIV-1 inhibitor modeled after AoT5Cyp, by fusing human CypA to human TRIM5 (hT5Cyp). Of 13 constructs, 3 showed substantial HIV-1–inhibitory activity when expressed in human cell lines. This activity required capsid binding by CypA and correlated with CypA linkage to the TRIM5a capsid-specificity determinant and the ability to form cytoplasmic bodies. CXCR4- and CCR5-tropic HIV-1 clones and primary isolates were inhibited from infecting multiple human macrophage and T cell lines and primary cells by hT5Cyp, as were HIV-2ROD, SIVAGMtan, FIVPET, and a circulating HIV-1 isolate previously reported to be AoT5Cyp resistant. The anti–HIV-1 activity of hT5Cyp was surprisingly more effective than that of the well-characterized rhesus TRIM5α, especially in T cells. hT5Cyp also blocked HIV-1 infection of primary CD4+ T cells and macrophages and conferred a survival advantage to these cells without disrupting their function. Extensive attempts to elicit HIV-1 resistance to hT5Cyp were unsuccessful. Finally, Rag2–/–γc–/– mice were engrafted with human CD4+ T cells that had been transduced by optimized lentiviral vectors bearing hT5Cyp. Upon challenge with HIV-1, these mice showed decreased viremia and productive infection in lymphoid organs and preserved numbers of human CD4+ T cells. We conclude that hT5Cyp is an extraordinarily robust inhibitor of HIV-1 replication and a promising anti–HIV-1 gene therapy candidate.