收稿日期: 2020-06-08
网络出版日期: 2021-05-14
基金资助
国家自然科学基金(81772194)
Inhibition of semen-derived enhancer of viral infection by superoxide dismutase
Received date: 2020-06-08
Online published: 2021-05-14
Supported by
National Natural Science Foundation of China(81772194)
目的·探究超氧化物歧化酶(superoxide dismutase,SOD)对精液来源的病毒增强因子(semen-derived enhancer of viral infection, SEVI)淀粉样纤维形成的抑制作用。方法·将440 μmol/L的前列腺酸性磷酸酶248-286(prostatic acid phosphatase 248-286,PAP248-286)多肽溶液或精液分别与不同活性水平的SOD混合孵育,于不同的时间点取样,用硫磺素T染色法、圆二色谱法、透射电子显微镜检测SOD对SEVI形成的影响;用病毒感染增强实验,检测SOD对SEVI促进人类免疫缺陷病毒1型(human immunodeficiency virus-1,HIV-1)感染能力的影响。灭活SOD并检测其对SEVI形成及病毒感染能力的影响。总SOD活性检测试剂盒检测5份健康志愿者精液中SOD的活性水平。结果·硫磺素T染色法结果显示,48 h时,46 U/mL和92 U/mL的SOD在体外可以抑制PAP248-286溶液形成SEVI淀粉样纤维;圆二色谱结果表明SOD可以抑制SEVI β-折叠结构的形成;透射电子显微镜结果也表明,SOD对SEVI的形成具有抑制作用。精液中的硫磺素T染色分析结果显示,SOD可抑制精液中的SEVI形成。病毒感染增强实验结果显示,SOD能够抑制SEVI促进HIV-1感染能力的作用。SOD灭活后上述作用均基本消失。5份健康男性精液中SOD活性分别为74.87、68.69、85.46、113.29、109.53 U/mL。结论·SOD在体外可以抑制SEVI淀粉样纤维的形成及其促进HIV-1感染的作用。
邱梦婕 , 李钊锋 , 黎奕斌 , 陈玉柳 , 程宏彦 , 刘叔文 , 谭穗懿 . 超氧化物歧化酶抑制精液来源的病毒增强因子形成的研究[J]. 上海交通大学学报(医学版), 2021 , 41(4) : 467 -472 . DOI: 10.3969/j.issn.1674-8115.2021.04.008
·To explore the inhibitory effect of superoxide dismutase (SOD) on the formation of semen-derived enhancer of viral infection (SEVI) amyloid fibrils.
·Prostatic acid phosphatase 248-286 (PAP248-286) at 440 μmol/L or seminal fluid was incubated with SOD at different activity levels, and at different time points, aliquots were taken from each sample for thioflavin T (ThT) staining, circular dichroism (CD) and transmission electron microscope (TEM) to detect the effect of SOD on the formation of SEVI. The effect of SOD on the ability of SEVI to promote human immunodeficiency virus-1 (HIV-1) infection was detected by virus infection enhancement experiment. The effects of inactivated SOD on the formation of SEVI and the ability of SEVI to promote virus infection were also detected. The SOD activity levels in the semen of five healthy volunteers were detected by using total SOD activity detection kit.
·The results of ThT staining showed that 46 U/mL and 92 U/mL SOD could inhibit the formation of SEVI fibrils in the PAP248-286 solution in vitro at 48-h time point. The results of CD showed that SOD could inhibit the formation of β-sheet structure of SEVI. The results of TEM also showed that SOD could inhibit the formation of SEVI. The ThT staining in the semen also demonstrated the inhibitory effect of SOD on the formation of SEVI. As shown in the virus infection enhancement experiment, SOD could inhibit the promoting effect of SEVI on HIV-1 infection. When SOD was inactivated, the effects above almost disappeared. The SOD activities in the semen of the five healthy males were 74.87, 68.69, 85.46, 113.29, and 109.53 U/mL, respectively.
·SOD can inhibit the formation of SEVI fibrils in vitro and the promoting effect of SEVI on HIV-1 infection.
1 | Duesberg PH. AIDS epidemiology: inconsistencies with human immunodeficiency virus and with infectious disease[J]. Proc Natl Acad Sci U S A, 1991, 88(4): 1575-1579. |
2 | Castellano LM, Shorter J. The surprising role of amyloid fibrils in HIV infection[J]. Biology (Basel), 2012, 1(1): 58-80. |
3 | Buvé A, Bishikwabo-Nsarhaza K, Mutangadura G. The spread and effect of HIV-1 infection in sub-Saharan Africa[J]. Lancet, 2002, 359(9322): 2011-2017. |
4 | Roan NR, Greene WC. A seminal finding for understanding HIV transmission[J]. Cell, 2007, 131(6): 1044-1046. |
5 | Münch J, Rücker E, St?ndker L, et al. Semen-derived amyloid fibrils drastically enhance HIV infection[J]. Cell, 2007, 131(6): 1059-1071. |
6 | Roan NR, Münch J, Arhel N, et al. The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection[J]. J Virol, 2009, 83(1): 73-80. |
7 | Li JQ, Yang ZC, Liu H, et al. ADS-J1 disaggregates semen-derived amyloid fibrils[J]. Biochem J, 2019, 476(6): 1021-1035. |
8 | Tan SY, Li JQ, Cheng HY, et al. The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1[J]. J Biol Chem, 2019, 294(37): 13740-13754. |
9 | Xun TR, Li WJ, Chen JQ, et al. ADS-J1 inhibits semen-derived amyloid fibril formation and blocks fibril-mediated enhancement of HIV-1 infection[J]. Antimicrob Agents Chemother, 2015, 59(9): 5123-5134. |
10 | Qiu MJ, Li ZF, Chen YL, et al. Tolcapone potently inhibits seminal amyloid fibrils formation and blocks entry of Ebola pseudoviruses[J]. Front Microbiol, 2020, 11: 504. |
11 | 蓝燕, 杨梓超, 刘涵, 等. PSB0739抑制精液来源的淀粉样纤维形成[J]. 南方医科大学学报, 2018, 38(11): 1338-1343. |
12 | 李锦清, 宋亚丽, 寻添荣, 等. 乳酸抑制精液来源淀粉样纤维的形成[J]. 南方医科大学学报, 2017, 37(7): 907-913. |
13 | 于平. 超氧化物歧化酶研究进展[J]. 生物学通报, 2006, 41(1): 4-6. |
14 | 袁牧, 王昌留, 王一斐, 等. 超氧化物歧化酶的研究进展[J]. 中国组织化学与细胞化学杂志, 2016, 25(6): 550-558. |
15 | Zhang HF, Zhao EY, Zhang CY, et al. The change of semen superoxide dismutase and acrosin activity in the sterility of male patients with positive antisperm antibody[J]. Cell Biochem Biophys, 2015, 73(2): 451-453. |
16 | Arisan ED, Arisan S, Kiremit MC, et al. Manganese superoxide dismutase polymorphism in chronic pelvic pain syndrome patients[J]. Prostate Cancer Prostatic Dis, 2006, 9(4): 426-431. |
17 | Eskiocak S, Gozen AS, Kilic AS, et al. Association between mental stress & some antioxidant enzymes of seminal plasma[J]. Indian J Med Res, 2005, 122(6): 491-496. |
18 | Mostafa T, Anis TH, El-Nashar A, et al. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele[J]. Int J Androl, 2001, 24(5): 261-265. |
19 | Akyol O, Ozbek E, Uz E, et al. Malondialdehyde level and total superoxide dismutase activity in seminal fluid from patients with varicocele[J]. Clin Exp Med, 2001, 1(1): 67-68. |
20 | 毛静, 郭润发, 朱文凯, 等. 男性精浆超氧化物歧化酶活性与各项精子参数间的关系[J]. 海南医学, 2019, 30(4): 451-454. |
21 | 陈金拳. SEVI淀粉样纤维结构形成的影响因素及抑制剂的研究[D]. 广州: 南方医科大学, 2015. |
22 | 李锦清. Suramin作为预防艾滋病多效杀微生物剂的研究[D]. 广州: 南方医科大学, 2017. |
23 | 金生浩, 吴梧桐. 肝素修饰人血超氧化物歧化酶稳定性研究[J]. 中国药科大学学报, 1994, 25(6): 373-375. |
24 | 曾仲奎, 张鹏飞, 鲍锦库, 等. 牛血超氧化物歧化酶在变性因素影响下的酶活与构象变化[J]. 四川大学学报(自然科学版), 1997, 34(4): 516-521. |
25 | Cole AM, Cole AL. Antimicrobial polypeptides are key anti-HIV-1 effector molecules of cervicovaginal host defense[J]. Am J Reproductive Immunol, 2008, 59(1): 27-34. |
26 | Tyssen D, Wang YY, Hayward JA, et al. Anti-HIV-1 activity of lactic acid in human cervicovaginal fluid[J]. mSphere, 2018, 3(4): e00055-18. |
27 | Madison MN, Roller RJ, Okeoma CM. Human semen contains exosomes with potent anti-HIV-1 activity[J]. Retrovirology, 2014, 11: 102. |
28 | Smith JA, Daniel R. Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle[J]. AIDS, 2016, 30(17): 2611-2616. |
29 | Nada HA, El-Shabrawy MM, Ibrahim SH, et al. Measurement of serum glutathione peroxidase, catalase and superoxide dismutase concentration in patients with external anogenital warts before and after treatment with intralesional tuberculin purified protein derivative[J]. Andrologia, 2020, 52(9): e13661. |
30 | Quaye O, Kuleape JA, Bonney EY, et al. Imbalance of antioxidant enzymes activities and trace elements levels in Ghanaian HIV-infected patients[J]. PLoS One, 2019, 14(7): e0220181. |
31 | Strycharz-Dudziak M, Fo?tyn S, Dworzański J, et al. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) in oropharyngeal cancer associated with EBV and HPV coinfection[J]. Viruses, 2020, 12(9): E1008. |
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