Anti-HIV activity of human defensin 5 in primary CD4+ T cells under serum-deprived conditions is a consequence of defensin-mediated cytotoxicity.
Anti-HIV activity of human defensin 5 in primary CD4+ T cells under serum-deprived conditions is a consequence of defensin-mediated cytotoxicity.
复制标题
DOI：
10.1371/journal.pone.0076038
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chang TL
中科院分区：
文献类型：
--
作者：
Ding J;Tasker C;Valere K;Sihvonen T;Descalzi-Montoya DB;Lu W;Chang TL
我们以前已经表明，人防御素5（HD 5）促进HIV感染的原代CD 4 + T细胞和HeLa细胞表达CD 4和CCR 5。HD 5是诱导性传播感染（STI），如沙眼衣原体和淋病奈瑟菌，这表明它在STI介导的增强艾滋病毒传播的作用。与我们的研究结果相反，最近的一项研究报告说，HD 5在缺乏血清的条件下在原代CD 4 + T细胞中具有抗HIV作用。为了解决这些明显矛盾的观察结果，我们研究了可能有助于HD 5对比效应的实验参数。血清剥夺培养条件与抗HIV活性。与HIV增强作用对HD 5结构的依赖性相反，在血清剥夺的原代CD 4 + T细胞中的抗HIV活性不依赖于HD 5结构，因为线性肽[Abu] HD 5表现出类似的抗HIV活性。在血清剥夺条件下，HD 5阻断了病毒进入之前或之后的CD 4受体非依赖性HIV-1vsv感染。我们发现，HD 5和其线性形式诱导显着的细胞死亡，在原代CD 4 + T细胞的血清剥夺培养条件下。HD 5介导的细胞凋亡，观察到早在2小时后加入防御素血清剥夺的主要CD 4 + T细胞。与原代CD 4 + T细胞相比，HD 5在无血清条件下不诱导细胞毒性并促进HeLa-CD 4-CCR 5细胞的HIV感染性。这些结果表明，在无血清培养条件下，HD 5对原代CD 4 + T细胞具有毒性，因此在数据解释中应谨慎。
We have previously shown that human defensin 5 (HD5) promotes HIV infectivity in both primary CD4+ T cells and HeLa cells expressing CD4 and CCR5. HD5 is induced in response to sexually transmitted infections (STIs) such as Chlamydia trachomatis and Neisseria gonorrhoeae, suggesting it plays a role in STI-mediated enhancement of HIV transmission. In contrast to our findings, a recent study reports that HD5 has an anti-HIV effect in primary CD4+ T cells under serum-deprived conditions. To resolve these apparently contradictory observations, we investigated experimental parameters that might contribute to contrasting effects of HD5. Serum-deprived culture conditions were associated with anti-HIV activity. In contrast to the dependence of the HIV enhancing effect on HD5 structure, the anti-HIV activity in serum-deprived primary CD4+ T cells was independent of HD5 structure as the linear peptide [Abu] HD5 exhibited similar anti-HIV activity. Under serum deprived conditions, HD5 blocked CD4-receptor-independent HIV-1vsv infection before or after viral entry. We found that HD5 and its linear form induced significant cell death in primary CD4+ T cells under serum-deprived culture conditions. HD5-mediated apoptosis was observed as early as 2 h after addition of defensins to serum-deprived primary CD4+ T cells. In contrast to primary CD4+ T cells, HD5 did not induce cytotoxicity and promote HIV infectivity of HeLa-CD4-CCR5 cells under serum-deprived conditions. These results indicate that under serum-deprived culture conditions HD5 is toxic for primary CD4+ T cells, warranting caution in data interpretation.
登录
查看更多内容
影响因子：
5.4
作者：
Guo, Jia;Wang, Weifeng;Wu, Yuntao
通讯作者：
Wu, Yuntao
影响因子：
4.4
作者：
Lehrer, Robert I.;Jung, Grace;Lu, Wuyuan
通讯作者：
Lu, Wuyuan
影响因子：
5.4
作者：
CHEN, BK;SAKSELA, K;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
5.3
作者：
Ding, Jian;Rapista, Aprille;Chang, Theresa L.
通讯作者：
Chang, Theresa L.
影响因子：
5.4
作者：
Guadalupe, M;Reay, E;Dandekar, S
通讯作者：
Dandekar, S