Inhibition of chikungunya virus replication by N-ω-Chloroacetyl-L-Ornithine in C6/36, Vero cells and human fibroblast BJ.

IF 1.3 4区 医学 Q4 INFECTIOUS DISEASES
Lucero Rojas-Luna, Araceli Posadas-Modragón, Amanda M Avila-Trejo, Verónica Alcántara-Farfán, Lorena I Rodríguez-Páez, José Angel Santiago-Cruz, Marvin O Pastor-Alonso, J Leopoldo Aguilar-Faisal
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引用次数: 0

Abstract

Background: Polyamines are involved in several cellular processes and inhibiting their synthesis affects chikungunya virus (CHIKV) replication and translation, and, therefore, reduces the quantity of infectious viral particles produced. In this study, we evaluated the inhibition of CHIKV replication by N-ω-chloroacetyl-L-ornithine (NCAO), a competitive inhibitor of ornithine decarboxylase, an enzyme which is key in the biosynthesis of polyamines (PAs).

Methods: The cytotoxicity of NCAO was evaluated by MTT in cell culture. The inhibitory effect of CHIKV replication by NCAO was evaluated in Vero and C6/36 cells. The intracellular polyamines were quantified by HPLC in CHIKV-infected cells. We evaluated the yield of CHIKV in titres via the addition of PAs in Vero, C6/36 cells and human fibroblast BJ treated with NCAO.

Results: We found that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p < 0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though it is predominantly spermidines and spermines which are present in infected cells. Inhibition of CHIKV replication was observed in human fibroblast BJ treated with 100 μM NCAO 24 h before and 48 h after the infection at a MOI 1.

Conclusions: NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero, C6/36 cells and human fibroblast BJ, suggesting that this compound is a possible antiviral agent for CHIKV.

N-ω-氯乙酰- l-鸟氨酸抑制基孔肯雅病毒在C6/36、Vero细胞和人成纤维细胞BJ中的复制。
背景:多胺参与多种细胞过程,抑制它们的合成影响基孔肯雅病毒(CHIKV)的复制和转译,因此减少传染性病毒颗粒的产生数量。在这项研究中,我们评估了N-ω-氯乙酰- l-鸟氨酸(NCAO)对CHIKV复制的抑制作用,NCAO是鸟氨酸脱羧酶的竞争性抑制剂,而鸟氨酸脱羧酶是多胺(PAs)生物合成的关键酶。方法:采用MTT法测定NCAO的细胞毒性。在Vero和C6/36细胞中评价NCAO对CHIKV复制的抑制作用。用高效液相色谱法测定了chikv感染细胞内的多胺含量。我们通过在NCAO处理的Vero细胞、C6/36细胞和人成纤维细胞BJ中添加PAs,评估了CHIKV的滴度产率。结果:我们发现NCAO抑制CHIKV在Vero和C6/36细胞中的复制呈剂量依赖性,使两种细胞系的PFU/mL降低至少4个对数(p < 0.01)。通过添加外源多胺,主要是腐胺,可以恢复病毒产量。高效液相色谱分析表明,NCAO降低了细胞内PAs的含量,尽管它主要是存在于感染细胞中的亚精胺和精胺。在感染前24 h和感染后48 h (MOI 1)下,100 μM NCAO对人成纤维细胞BJ的复制有抑制作用。结论:NCAO通过消耗细胞内多胺在Vero、C6/36细胞和人成纤维细胞BJ中抑制CHIKV复制,提示该化合物可能是一种抗病毒药物。
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来源期刊
Antiviral Therapy
Antiviral Therapy 医学-病毒学
CiteScore
2.60
自引率
8.30%
发文量
35
审稿时长
4-8 weeks
期刊介绍: Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases. The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.
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