Activity of curcumin against human cytomegalovirus infection<i> in vitro</i>_Journal of Biomedical Engineering

Authors：

DING Xiang ¹ , YUE Jirong ¹ , DONG Birong ¹ ,  Sean X. LENG ²

1. The Center of Gerontology and Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, P. R. China;
2. Division of Geriatric Medicine and Gerontology and Center on Aging and Immune Remodeling trisodium phosphonoformate, Department of Medicine, Johns Hopkins University School of Medicine, Maryland 21224, USA;

Corresponding author：

Sean X. LENG, Email: sleng1@jhu.edu

Keywords：

Human cytomegalovirus; Curcumin; In vitro experiment

DOI：

10.7507/1001-5515.202108035

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This study aimed to investigate the effect of curcumin (Cur) against human cytomegalovirus (HCMV) in vitro. Human embryonic lung fibroblasts were cultured in vitro. The tetrazolium salt (MTS) method was used to detect the effects of Cur on cell viability. The cells were divided into control group, HCMV group, HCMV + (PFA) group and HCMV + Cur group in this study. The cytopathic effect (CPE) of each group was observed by plaque test, then the copy number of HCMV DNA in each group was detected by quantitative polymerase chain reaction (qPCR), and the expression of HCMV proteins in different sequence was detected by Western blot. The results showed that when the concentration of Cur was not higher than 15 μmol/L, there was no significant change in cell growth and viability in the Cur group compared with the control group (P>0.05). After the cells were infected by HCMV for 5 d, the cells began to show CPE, and the number of plaques increased with time. Pretreatment with Cur significantly reduced CPE in a dose-dependent manner. After the cells were infected by HCMV, the DNA copy number and protein expression gradually increased in a time-dependent manner. Pretreatment with Cur significantly inhibited HCMV DNA copies and downregulate HCMV protein expression levels in a concentration-dependent manner, and the difference was statistically significant (P<0.05). In conclusion, Cur may exert anti-HCMV activity by inhibiting the replication of HCMV DNA and down-regulating the expression levels of different sequence proteins of HCMV. This study provides a new experimental basis for the development of anti-HCMV infectious drugs.

Citation： DING Xiang, YUE Jirong, DONG Birong, Sean X. LENG. Activity of curcumin against human cytomegalovirus infection in vitro. Journal of Biomedical Engineering, 2022, 39(6): 1158-1164. doi: 10.7507/1001-5515.202108035 Copy

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6.	Rubin R H, Tolkoff-Rubin N E, Oliver D, et al. Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal transplantation. Transplantation, 1985, 40(3): 243-249.
7.	Jacobson M A, Mills J. Serious cytomegalovirus disease in the acquired im¬munodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Ann Intern Med, 1988, 108(4): 585-594.
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9.	Jergovic M, Contreras N A, Nikolich-Zugich J. Impact of CMV upon immune aging: facts and fiction. Med Microbiol Immunol, 2019, 208(3-4): 263-269.
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15.	Aiello A E, Haan M N, Pierce C M, et al. Persistent infection, inflammation, and functional impairment in older Latinos. J Gerontol A Biol Sci Med Sci, 2008, 63(6): 610-618.
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17.	Gkrania-Klotsas E, Langenberg C, Sharp S J, et al. Seropositivity and higher immunoglobulin G antibody levels against cytomegalovirus are associated with mortality in the population based European prospective investigation of Cancer–Norfolk cohort. Clin Infect Dis, 2013, 56(10): 1421-1427.
18.	Griffiths P D. The treatment of cytomegalovirus infection. J Antimicrob Chemother 2002; 49(2): 243-253.
19.	Yang C, Su X, Liu A, et al. Advances in clinical study of curcumin. Curr Pharm Des, 2013, 19(11): 1966-1973.
20.	商玮,蔡辉. 姜黄素对免疫细胞及细胞因子的作用研究进展. 江苏中医药, 2008, 40(4): 92-94.
21.	Lv Y L, Lan A J, Lan Y Y, et al. Activity of curcumin against human cytomegalovirus in vitro. Afr J of Pharm Pharma, 2012, 6(1): 30-35.
22.	Lv Yali, Lei Ning, Wang Dan, et al. Protective effect of curcumin against cytomegalovirus infection in Balb/c mice. Environ Toxicol Pharmacol, 2014, 37(3): 1140-1147.
23.	He Y, Yue Y, Zheng X, et al. Curcumin, inflammation, and chronic diseases: how are they linked?. Molecules, 2015, 20(5): 9183-9213.
24.	Song Y, Ge W, Cai H, et al. Curcumin protects mice from coxsackievirus B3-induced myocarditis by inhibiting the phosphatidylinositol 3 kinase /Akt /nuclear factor-κB Pathway. J Card Pharm Ther, 2013, 18(6): 560-569.
25.	Chen M H, Lee M Y, Chuang J J, et al. Curcumin inhibits HCV replication by induction of heme oxygenase-1 and suppression of AKT. Int J Mol Med, 2012, 30(5): 1021-1028.
26.	Mishra A, Kumar R, Tyagi A, et al. Curcumin modulates cellular AP-1,NF-κB,and HPV16 E6 proteins in oral cancer. Ecanc, 2015, 9: 525-536.
27.	Han S, Xu J, Guo X, et al. Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production. Clin Exper Pharm Physi, 2017, 45(1): 84-93.
28.	范世珍, 王文杰, 于波海. 姜黄素抗病毒作用研究进展. 现代中西医结合杂志, 2020, 29(24): 2734-2736.
29.	Lv Y L, An Z L, Chen H, et al. Mechanism of curcumin resistance to human cytomegalovirus in HELF cells. BMC Complement Altern Med, 2014, 14: 284.
30.	Pari G S. Nuts and bolts of human cytomegalovirus lytic DNA replication. Curr Top Microbiol Immunol, 2008, 325: 153-166.
31.	Arvin A M, Campadelli-Fiume G, Mocarsky E S. Human herpesviruses: biology, therapy and immunoprophylaxis. Cambridge: Cambridge Press, 2007: 204-230.

1. Griffiths P, Baraniak I, Reeves M. The pathogenesis of human cytomegalovirus. J Pathol, 2015, 235(2): 288-297.
2. Cannon M J, Schmid D S, Hyde T B. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol, 2010, 20(4): 202-213.
3. Staras S A, Dollard S C, Radford K W, et al. Seroprevalence of cytomegalovirus infection in the United States, 1988-1994. Clin Infect Dis, 2006, 43(9): 1143-1151.
4. Sissons J G, Carmichael A J. Clinical aspects and management of cytomegalovirus infection. J Infect, 2002, 44(2): 78-83.
5. Ho M. The history of cytomegalovirus and its diseases. Med Microbiol Immunol, 2008, 197(2): 65-73.
6. Rubin R H, Tolkoff-Rubin N E, Oliver D, et al. Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal transplantation. Transplantation, 1985, 40(3): 243-249.
7. Jacobson M A, Mills J. Serious cytomegalovirus disease in the acquired im¬munodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Ann Intern Med, 1988, 108(4): 585-594.
8. Winston D J, Ho W G, Champlin R E. Cytomegalovirus infections after allogeneic bone marrow transplantation. Rev Infect Dis, 1990, 12(Suppl7): S776-S792.
9. Jergovic M, Contreras N A, Nikolich-Zugich J. Impact of CMV upon immune aging: facts and fiction. Med Microbiol Immunol, 2019, 208(3-4): 263-269.
10. Zhu W B, Liu S Q. The role of human cytomegalovirus in atherosclerosis: a systematic review. Acta Biochim Biophys Sin, 2020, 52(4): 339-353.
11. Roberts B W, Cech I. Association of type 2 diabetes mellitus and seroprevalence for cytomegalovirus. South Med J, 2005, 98(7): 686-692.
12. Wang Z, Peng X, Li M, et al. Is human cytomegalovirus infection associated with essential hypertension? A meta-analysis of 11, 878 participants. J Med Virol, 2016, 88(5): 852-858.
13. Ciccocioppo R, Racca F, Scudeller L, et al. Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease. Immunol Res, 2016, 64(1): 191-203.
14. Aiello A E, Haan M N, Blythe L, et al. The influence of latent viral infection on rate of cognitive decline over 4 years. J Am Geriatr Soc, 2006, 54(7): 1046-1054.
15. Aiello A E, Haan M N, Pierce C M, et al. Persistent infection, inflammation, and functional impairment in older Latinos. J Gerontol A Biol Sci Med Sci, 2008, 63(6): 610-618.
16. Wang G C, Kao W H L, Murakami P, et al. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol, 2010, 171(10): 1144-1152.
17. Gkrania-Klotsas E, Langenberg C, Sharp S J, et al. Seropositivity and higher immunoglobulin G antibody levels against cytomegalovirus are associated with mortality in the population based European prospective investigation of Cancer–Norfolk cohort. Clin Infect Dis, 2013, 56(10): 1421-1427.
18. Griffiths P D. The treatment of cytomegalovirus infection. J Antimicrob Chemother 2002; 49(2): 243-253.
19. Yang C, Su X, Liu A, et al. Advances in clinical study of curcumin. Curr Pharm Des, 2013, 19(11): 1966-1973.
20. 商玮,蔡辉. 姜黄素对免疫细胞及细胞因子的作用研究进展. 江苏中医药, 2008, 40(4): 92-94.
21. Lv Y L, Lan A J, Lan Y Y, et al. Activity of curcumin against human cytomegalovirus in vitro. Afr J of Pharm Pharma, 2012, 6(1): 30-35.
22. Lv Yali, Lei Ning, Wang Dan, et al. Protective effect of curcumin against cytomegalovirus infection in Balb/c mice. Environ Toxicol Pharmacol, 2014, 37(3): 1140-1147.
23. He Y, Yue Y, Zheng X, et al. Curcumin, inflammation, and chronic diseases: how are they linked?. Molecules, 2015, 20(5): 9183-9213.
24. Song Y, Ge W, Cai H, et al. Curcumin protects mice from coxsackievirus B3-induced myocarditis by inhibiting the phosphatidylinositol 3 kinase /Akt /nuclear factor-κB Pathway. J Card Pharm Ther, 2013, 18(6): 560-569.
25. Chen M H, Lee M Y, Chuang J J, et al. Curcumin inhibits HCV replication by induction of heme oxygenase-1 and suppression of AKT. Int J Mol Med, 2012, 30(5): 1021-1028.
26. Mishra A, Kumar R, Tyagi A, et al. Curcumin modulates cellular AP-1,NF-κB,and HPV16 E6 proteins in oral cancer. Ecanc, 2015, 9: 525-536.
27. Han S, Xu J, Guo X, et al. Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production. Clin Exper Pharm Physi, 2017, 45(1): 84-93.
28. 范世珍, 王文杰, 于波海. 姜黄素抗病毒作用研究进展. 现代中西医结合杂志, 2020, 29(24): 2734-2736.
29. Lv Y L, An Z L, Chen H, et al. Mechanism of curcumin resistance to human cytomegalovirus in HELF cells. BMC Complement Altern Med, 2014, 14: 284.
30. Pari G S. Nuts and bolts of human cytomegalovirus lytic DNA replication. Curr Top Microbiol Immunol, 2008, 325: 153-166.
31. Arvin A M, Campadelli-Fiume G, Mocarsky E S. Human herpesviruses: biology, therapy and immunoprophylaxis. Cambridge: Cambridge Press, 2007: 204-230.

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Activity of curcumin against human cytomegalovirus infection in vitro

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