Paradoxical effects of two theta-defensins on HIV type 1 infection.
Paradoxical effects of two theta-defensins on HIV type 1 infection.
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两种 θ 防御素对 HIV 1 型感染的矛盾作用。
DOI：
10.1089/aid.2006.0119
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发表时间：
2007
影响因子：
1.5
通讯作者：
Pang,Shen
中科院分区：
文献类型：
--
作者：
Wang,Qiuwei;Wang,Wei;Zheng,Junying;Tabibian,Sina;Xie,Yiming;Song,Jun;Waring,AlanJ;Chiu,Robert;Yang,OttoO;Chen,IrvinSY;Lehrer,RobertI;Pang,Shen
逆转录周期蛋白-1 （RC-100）是一种环状八肽，其主要结构基于表达的人源θ-防御素假基因的序列。RC-111与RC-100具有相同的氨基酸序列，也是环状的，但它的残基沿着肽的主链以相反的顺序排列。我们利用表达绿色荧光蛋白的HIV克隆，量化了RC-100和RC-111对HIV-1感染的影响。而0.2 μg/ml的RC-100对cd4阳性细胞的感染抑制作用约为80%，其逆转录类似物显著增强了细胞的感染。RC-100和RC-111在cd4阴性细胞的HIV感染中也有作用。40 ng/ml的RC-111显著增强cd4阴性细胞对HIV-1的感染，而浓度约为10 μg/ml的RC-100显著抑制HIV感染。rc - 1110x是RC-111的一种无环变体，具有β-发夹结构，也能增强HIV-1感染，但效果不如环状RC-111。RC-100和RC-111的不同作用表明，θ-防御素肽的拓扑结构和极性决定了它们对HIV感染的影响。RC-111增强HIV-1感染的能力可能有助于开发能够增强hiv慢病毒载体基因传递的肽。
Retrocyclin-1 (RC-100) is a cyclic octadecapeptide whose primary structure is based on the sequence of an expressed humanθ-defensin pseudogene. RC-111 has the same amino acid sequence as RC-100 and is also cyclic, but its residues are placed in reverse order along the peptide's backbone. We quantified the effects of RC-100 and RC-111 on HIV-1 infection using HIV clones that expressed green fluorescent protein. Whereas 0.2 μg/ml of RC-100 inhibited infection of CD4-positive cells by approximately 80%, its retroanalogue significantly enhanced infection of the cells. RC-100 and RC-111 also demonstrate their effects in HIV infection of CD4-negative cells. Whereas 40 ng/ml of RC-111 significantly enhanced infection of CD4-negative cells by HIV-1, RC-100 demonstrated significant inhibition of HIV infection with a concentration of approximately 10 μg/ml. RC-111ox, an acyclic variant of RC-111 with a β-hairpin structure, also enhanced HIV-1 infection, but did so less effectively than cyclic RC-111. The divergent actions of RC-100 and RC-111 show that topology and polarity ofθ-defensin peptides can determine their effect on HIV infection. The ability of RC-111 to enhance HIV-1 infection might prove useful in developing peptides that can enhance gene delivery by HIV-based lentiviral vectors.