Knock out and kill
A group of researchers from the University of California at Los Angeles has improved a method developed in 2017 to destroy HIV-infected cells. In case of further success, it will help to reduce the amount of the virus or even completely eliminate it in the body of infected people.
According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), there are currently 38 million people living with HIV worldwide, and it is estimated that in the decades since the virus began spreading, 36 million have died from diseases associated with this virus.
HIV carriers take antiretroviral drugs to keep the virus "in check". But it has the ability to elude antiretroviral therapy by hiding in CD4+ T-lymphocytes, which signal another type of T-lymphocytes, CD8, about the destruction of HIV-infected cells. When an HIV-infected person stops treatment, the virus exits these reservoirs and multiplies in the body, weakening the immune system and increasing the likelihood of opportunistic infections or cancer.
The researchers have strengthened their previously developed "hit and kill" strategy, forcing the virus dormant in infected cells to manifest itself so that it can be detected and destroyed. In the first study, mice genetically modified to simulate the human immune system were infected with HIV. Then they were given antiretroviral therapy, and after that they were injected with synthetic briostatin SUW133, which was developed at Stanford University to "wake up" HIV mice. Up to 25% of previously inactive reservoir cells began to express HIV and were destroyed within 24 hours. But a more effective way to kill cells with HIV was needed.
In the new study, mouse models also received antiretroviral therapy and then SUW133 to activate HIV in infected cells. To destroy these cells, mice were injected with healthy natural killer cells (NK cells). The combination of SUW133 and injections of healthy NK cells in 40% of HIV-infected mice led to a complete recovery.
The researchers also analyzed the spleen of mice, since it contains immune cells, including HIV-infected cells, and did not find a virus there, which means that the HIV reservoir cells were destroyed. In addition, the combined approach was more effective than each of its stages (antiretroviral therapy, SUW133, NK cells) separately.
The next goal of the researchers is to improve the approach to eliminate HIV in 100% of mice in future experiments. They will also be working on preclinical studies in primates with the ultimate goal of testing the same approach in humans.
Article by J.T.Kim et al. Latency reversal plus natural killer cells diminish HIV reservoir in vivo is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on UCLA materials: UCLA-led team refines 'kick and kill' strategy aimed at eliminating HIV-infected cells.