Synthetic Host Defense Peptides Inhibit Venezuelan Equine Encephalitis Virus Replication and the Associated Inflammatory Response.
Synthetic Host Defense Peptides Inhibit Venezuelan Equine Encephalitis Virus Replication and the Associated Inflammatory Response.
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DOI：
10.1038/s41598-020-77990-3
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发表时间：
2020-12-08
影响因子：
4.6
通讯作者：
Narayanan A
中科院分区：
文献类型：
--
作者：
Ahmed A;Bakovic A;Risner K;Kortchak S;Der Torossian Torres M;de la Fuente-Nunez C;Lu T;Bhalla N;Narayanan A
委内瑞拉马脑炎病毒（VEEV）是披膜病毒科病毒的一种新世界甲病毒，其在人类和马中引起疾病的周期性爆发。VEEV感染后的疾病表现为具有流感样症状的发热性疾病，在少数情况下可进展为脑炎并导致永久性神经系统后遗症。VEEV被归类为B类选择因子，因为其易于雾化，并且在气雾剂形式下具有高的感染性。目前，没有FDA批准的疫苗或治疗剂可用于对抗VEEV感染。体内VEEV感染的特征在于广泛的全身性炎症，其可通过潜在地增加非现场细胞对病毒感染和传播的易感性来加剧感染。因此，靶向感染和相关炎症的治疗剂代表了未满足的需求。我们以前已经证明，宿主防御肽（HDPs），短肽的先天免疫反应的关键组成部分，表现出抗病毒活性对多种病毒，包括VEEV。在这项研究中，我们设计了合成肽indolicidin，天然存在的HDP，并测试其对VEEV的疗效。两种候选合成肽抑制VEEV复制约1000倍，并在基因和蛋白表达水平上降低炎症介质如IL 1 α、IL 1 β、IFNγ和TNFα的表达。此外，还观察到参与白细胞趋化性的基因和IL 1RN等抗炎基因的表达水平增加。总之，我们得出结论，我们的合成肽抑制VEEV复制和与VEEV感染相关的炎症负荷。
Venezuelan equine encephalitis virus (VEEV), a New World alphavirus of the Togaviridae family of viruses causes periodic outbreaks of disease in humans and equines. Disease following VEEV infection manifests as a febrile illness with flu-like symptoms, which can progress to encephalitis and cause permanent neurological sequelae in a small number of cases. VEEV is classified as a category B select agent due to ease of aerosolization and high retention of infectivity in the aerosol form. Currently, there are no FDA-approved vaccines or therapeutics available to combat VEEV infection. VEEV infection in vivo is characterized by extensive systemic inflammation that can exacerbate infection by potentially increasing the susceptibility of off-site cells to infection and dissemination of the virus. Hence, a therapeutic targeting both the infection and associated inflammation represents an unmet need. We have previously demonstrated that host defense peptides (HDPs), short peptides that are key components of the innate immune response, exhibit antiviral activity against a multitude of viruses including VEEV. In this study, we designed synthetic peptides derived from indolicidin, a naturally occurring HDP, and tested their efficacy against VEEV. Two candidate synthetic peptides inhibited VEEV replication by approximately 1000-fold and decreased the expression of inflammatory mediators such as IL1α, IL1β, IFNγ, and TNFα at both the gene and protein expression levels. Furthermore, an increase in expression levels of genes involved in chemotaxis of leukocytes and anti-inflammatory genes such as IL1RN was also observed. Overall, we conclude that our synthetic peptides inhibit VEEV replication and the inflammatory burden associated with VEEV infection.
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DOI：
10.1016/j.bbamem.2014.04.015
发表时间：
2014-09
期刊：
Biochimica et biophysica acta
影响因子：
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影响因子：
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