Newton001 The dependency of HIV-1 and dengue virus infections on host metabolism as novel targets for antiviral therapy.

Newton001 HIV-1 和登革热病毒感染对宿主代谢的依赖性作为抗病毒治疗的新靶标。

• 批准号: MR/P502054/1
• 负责人: Hendrik Huthoff
• 金额: $ 1.38万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP502054%2F1
• 关键词: Newton001; dependency; HIV; dengue; virus

Infectious diseases account for a vast proportion of deaths and disabilities worldwide. Brazil has a very high incidence of dengue with a total of 1,453,786 reported cases of infection and 235 deaths in 2013. In addition, 730,000 people living with human immunodeficiency virus type 1 (HIV-1) infection were recorded in Brazil in 2013. With a prevalence of 0.6% of adults being infected with HIV-1, Brazil has twice the incidence of HIV-1 as is the average in developed nations, such as the UK. There are no specific treatments for dengue, nor vaccines for either dengue virus or HIV-1. Life-long antiretroviral therapy is effective in controlling HIV-1, but side effects and emergence of viral drug resistance are commonplace. Thus, new antivirals that target dengue virus or HIV-1 are needed and would have the potential to benefit countries that are particularly burdened by these infections, such as Brazil. All viruses are devoid of the metabolic machinery to provide the resources to fuel virus replication. Therefore, viruses are dependent on host metabolism and this may provide an "achilles heel" for drug development. Metabolism is an area that has attracted attention for developing anti-cancer therapies because cancers are associated with metabolic alterations. Targeting the host metabolism instead of viral components would circumvent the emergence of drug resistant viruses. This project sets out to map the dependency of dengue virus and HIV-1 on cellular metabolism to inform the development of novel antiviral therapies.

传染病在全世界的死亡和残疾中占很大比例。巴西的登革热发病率非常高，2013年共报告了1，453，786例感染病例和235例死亡。此外，2013年巴西记录了730 000名1型人类免疫缺陷病毒（艾滋病毒-1）感染者。巴西成年人感染HIV-1的患病率为0.6%，是英国等发达国家平均水平的两倍。目前还没有针对登革热的特异性治疗方法，也没有针对登革热病毒或HIV-1的疫苗。终身抗逆转录病毒疗法在控制HIV-1方面是有效的，但副作用和病毒耐药性的出现是常见的。因此，需要针对登革热病毒或HIV-1的新的抗病毒药物，并有可能使巴西等受这些感染负担特别重的国家受益。所有的病毒都缺乏代谢机制来提供病毒复制所需的资源。因此，病毒依赖于宿主代谢，这可能为药物开发提供了“阿喀琉斯之踵”。由于癌症与代谢改变有关，因此代谢是开发抗癌疗法的一个领域。靶向宿主代谢而不是病毒成分将避免耐药病毒的出现。该项目旨在绘制登革病毒和HIV-1对细胞代谢的依赖性，为新型抗病毒疗法的开发提供信息。

项目成果

Upregulation of Glucose Uptake and Hexokinase Activity of Primary Human CD4+ T Cells in Response to Infection with HIV-1.

原代人 CD4+ T 细胞响应 HIV-1 感染的葡萄糖摄取和己糖激酶活性上调。

• DOI: 10.3390/v10030114
• 发表时间: 2018-03-07
• 期刊: Viruses
• 作者: Kavanagh Williamson M;Coombes N;Juszczak F;Athanasopoulos M;Khan MB;Eykyn TR;Srenathan U;Taams LS;Dias Zeidler J;Da Poian AT;Huthoff H
• 通讯作者: Huthoff H