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

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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.