A new approach taking advantage of HIV's sweet tooth may keep the virus from replicating in human cells, at least in vitro, according to research by scientists at Northwestern University in Chicago, Illinois, and Vanderbilt University in Nashville, Tennessee.
The study, published in PLOS Pathogens, tested a compound that targets the sugar and nutrient supply HIV needs to survive. The same mechanism could also be used to prevent cancer cells from spreading.
The human body uses CD4+ cells to fight pathogens. These CD4+ cells become active when the body detects a potentially harmful invader, such as a cold virus or HIV. A component in activated CD4+ cells, PLD1 (phospholipase D1), signals them to store up sugar and nutrients in order to fight the invader. If that invader is HIV, it takes over all that stored sugar and starts to replicate itself, and also triggers the activation and growth of additional CD4+ cells.
The newly developed compound blocks PLD1, which in turn stops the activated CD4+ cells from storing sugar, and thereby deprives HIV of the nutrients it needs. This process not only prevents HIV from making copies of itself, it also keeps the growth of excess CD4+ cells in check. Otherwise those extra cells could lead to persistent inflammation, which in turn causes premature organ damage in those living with HIV.
"Perhaps this new approach, which slows the growth of the immune cells, could reduce the dangerous inflammation and thwart the life-long persistence of HIV," said lead study author Harry Taylor, Ph.D., of Northwestern University's Feinberg School of Medicine.
Cancer cells use the same PLD1 signal to accumulate the nutrients they need to spread. In fact, the compound used in the HIV study was first identified during breast cancer research at Vanderbilt, where Taylor previously taught. He hopes to identify additional compounds that could be developed into medications to prevent HIV -- and perhaps also cancer -- replication.
This is not the first time the same drugs have been studied against both cancer and HIV. Protease inhibitors, a mainstay of many HIV treatment regimens, have been investigated for the treatment of certain cancers; and the first HIV drug approved in the U.S., Retrovir (zidovudine, AZT), was also studied as an anti-cancer agent.
"This discovery opens new avenues for further research to solve today's persisting problems in treating HIV infection: avoiding virus resistance to medicines, decreasing the inflammation that leads to premature aging, and maybe even one day being able to cure HIV infection," said Richard D'Aquila, M.D., director of Northwestern's HIV Translational Research Center.