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

传染病占全世界死亡和残疾的很大比例。巴西的登革热发病率非常高，2013年报告的感染病例总数为1,453,786例，死亡235例。此外，2013年巴西记录了730,000名人类免疫缺陷病毒1型(HIV-1)感染者。巴西成年人感染HIV-1的流行率为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效药，也没有针对登革热病毒或HIV-1的疫苗。终生抗逆转录病毒疗法对控制HIV-1有效，但副作用和出现病毒耐药性是司空见惯的。因此，需要针对登革热病毒或艾滋病毒-1的新的抗病毒药物，并有可能使巴西等特别受这些感染影响的国家受益。所有病毒都缺乏为病毒复制提供资源的新陈代谢机制。因此，病毒依赖于宿主的新陈代谢，这可能会为药物开发提供“阿喀琉斯之跟”。新陈代谢是开发抗癌疗法而引起人们关注的一个领域，因为癌症与新陈代谢变化有关。以宿主代谢为目标，而不是病毒成分，将绕过抗药性病毒的出现。该项目旨在绘制登革热病毒和HIV-1对细胞新陈代谢的依赖图，为新的抗病毒疗法的开发提供信息。

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.