Inhibition of Marek's Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro.

Inhibition of Marek's Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro.
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DOI:
10.3390/v15081652
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发表时间:
2023-07-29
期刊:
Viruses
影响因子:
--
通讯作者:
Behboudi S
Behboudi S
中科院分区:
其他
文献类型:
--
作者:
Kamble N;Reddy VRAP;Jackson B;Anjum FR;Ubachukwu CC;Patil A;Behboudi S

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马立克氏病病毒(MDV)在鸡中引起一种致命的淋巴细胞增生性疾病,给家禽业造成巨大的经济损失。有人认为,MDV抑制I型干扰素的诱导,从而逃脱免疫控制。胆固醇25-羟化酶(CH25H)是一种已知具有抗病毒活性的干扰素刺激基因(ISG),其编码的酶可将胆固醇催化为25-羟基胆固醇(25-HC)。其他氧甾醇,如27-羟基胆固醇(27-HC),也被证明具有抗病毒活性,27-HC是通过细胞色素P450酶氧化酶甾醇27-羟化酶A1 (CYP27A1)在胆固醇的催化下合成的。在感染后24小时(hpi), MDV刺激了I型干扰素(IFN-α)反应,在48和72 hpi时显著降低,使用鸡I型IFN荧光素酶测定。然后,利用RT-PCR,我们证实了鸡I型IFN (IFN-α)上调鸡胚成纤维细胞(CEF)中CH25H和CYP27A1基因。同时,我们的研究结果表明,在mdv感染的CEF细胞中,CH25H在48 hpi和CYP27A1在72hpi处有适度和短暂的上调。在体外用25-HC或27-HC处理的CEFs中,MDV滴度和斑块大小显着降低,正如使用MDV的标准斑块测定所证明的那样。综上所述,我们的研究结果表明25-HC和27-HC可能是有效的抗病毒药物,可以控制MDV的复制和传播。
Marek’s disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.
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影响因子: 3.7
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DOI: 10.1128/iai.12.5.1058-1064.1975
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发表时间: 1984-01-01
期刊: AVIAN DISEASES
影响因子: 1.4
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