Weigh! Two pieces of nature reveal new strategies to reverse HIV latency

January 23, 2020 / Biovalley BIOON / - -- about 38 million people around the world are infected with HIV, and about 1.1 million people in the United States are infected with the virus Currently, people with HIV are treated with antiretroviral drugs (Art), which can suppress HIV to undetectable levels in the blood, but the virus persists in static CD4 + T cells with latent infection The immune system can't recognize these cells, and there's no therapy available to eliminate them After stopping art treatment, HIV load will increase This is why people with HIV must continue to take art drugs, and this latent HIV virus library is considered to be the biggest obstacle to cure HIV infection Now, in the first new study, researchers from the University of North Carolina at Chapel Hill and the University of Emory in the United States use a compound called azd5582 to activate CD4 + T cells in blood and many different tissues that are potentially infected with HIV, which is at impressive levels and has little or no toxicity The related research results were published online in the journal Nature on January 22, 2020 The title of the paper is "systematic HIV and SIV latency reversal via non canonical NF - κ B signaling in vivo" When the immune cells suffering from latent HIV infection are reactivated, the cells begin to produce HIV particles (red), which sprout and release from the cells (blue), pictured in NIAID The pioneering study was carried out by researchers at the University of North Carolina Chapel Hill School of medicine in a mouse model with fully functional human immune cells that are HIV infected and inhibited by art drugs Importantly, the study was subsequently expanded in a longitudinal multi dose experiment at Emory University In this longitudinal multi dose experiment, rhesus monkeys infected with simian immunodeficiency virus (SIV) and can be inhibited by art drugs were studied Qura therapeutics, in collaboration with the University of North Carolina at Chapel Hill and Viiv healthcare, has carried out basic scientific research, thus speeding up research in animal models More research is needed before testing can begin in the human body, but this research is considered an important scientific step towards the development of cures Dr J Victor Garcia, co-author of the paper and professor of Microbiology and immunology at the University of North Carolina Chapel Hill School of medicine, said, "before that, no one has successfully tested a latent reversal molecule in human or animal models carrying human cells, and has proved that it can be used in peripheral blood and static CD4 from multiple tissues+ T cells showed systematic HIV activation, which was then replicated in a completely different species (macaques) infected with another virus (SIV) " Dr Ann chahroudi, associate professor of pediatrics at Emory University and director of the center for children's infection and vaccine at Emory University, co-author of the paper, said, "azd5582 can significantly reactivate latent SIV in quiescent CD4 + T cells, and significantly induce the continuous production of SIV in blood when these rhesus monkeys are still receiving art treatment every day This is an exciting scientific achievement, and we hope it will be an important step towards eradicating HIV in people living with HIV one day " For several years, scientists have been trying various latent reversals to lure HIV out of its incubation period, making it visible to the immune system, allowing an antiviral immune response to kill cells infected with the virus Some latent reversals focus on activating the classical NF KB pathway in CD4 + T cells, so as to make virus infected cells out of the incubation period But activating the classic NF KB pathway involves hundreds of genes, which makes this radical approach produce too many side effects Qura therapeutics scientists turned their attention to the non classical NF KB pathway in CD4 + T cells Dr Richard Dunham, co-author of the paper, chief researcher of Qura therapeutics and director of HIV cure of VIV healthcare, conducted necessary research on patients' cells, and found that as a second mitochondrial activator of caspases, Azd5582 is an effective latent reversal agent Azd5582 can gradually and persistently activate the nonclassical NF KB pathway, and it can activate fewer human genes than other latent reversal agents, thus potentially making it less toxic "We are excited that for the first time, we now have an easy-to-use tool to test the long-standing assumption that activating latent HIV can expose the HIV virus pool," Dunham said Garcia and her researchers at the University of North Carolina, Chapel Hill, then tested azd5582 in a mouse model that contained human CD4 + T cells that could be infected with HIV and inhibited by art They recorded an increase in HIV RNA expression in the blood and in almost all tissues, including lymph nodes, thymus, bone marrow, liver, lungs and brain In some cases, HIV RNA has increased more than 20 fold At Emory University, chahroudi and his colleagues tested azd5582 in rhesus monkeys infected with SIV and inhibited by art They were given multiple doses of azd5582 once a week, and then found similar results They observed a surge in SIV RNA expression in the lymph nodes and blood of these rhesus monkeys, marking the first time that a latent reversal agent has accomplished this feat in two animal models, with little toxicity In the second new study, Dr Guido Silvestri and researchers at Emory University led by chahroudi worked with researchers at the University of North Carolina at Chapel Hill to achieve a latent reversal in a different way The related research results were published online in the journal Nature on January 22, 2020, and the title of the paper is "robot and persistent reactivation of SIV and HIV by n-803 and completion of CD8 + cells" They injected an antibody into non-human primates infected with HIV and inhibited by art to remove CD8 + T cells, which play a very important role in controlling virus infection They then gave an improved version of the cytokine IL-15, and found that the combination resulted in the presence of SIV RNA in previously unseen blood and tissues For HIV, they found similar results in the same mouse model that had been tested for azd5582 Although it is not clear whether the strategy to clear CD8 + T cells is suitable for humans, this result opens up a new way to understand how to control HIV and how to manipulate its RNA expression All in all, these findings show the power of different research teams, different research institutions and academia industry cooperation The two studies confirmed in different model systems that HIV can be removed from its latent state by using a latent reversal agent, which provides the possibility to develop new therapies that may one day cure HIV infection (bio Com) reference: 1 Christopher C Nixon et al Systematic HIV and SIV latency reversal via non canonical NF - κ B signaling in vivo Nature, 2020, DOI: 10.1038/s41586-020-1951-3 2 Julia bergild McBrien et al Robot and persistent reactivation of SIV and HIV by n-803 and completion of CD8 + cells Nature, 2020, doi:10.1038/s41586-020-1946-0 3.Researchers reverse HIV latency, important scientific step toward cure https://medicalxpress.com/news/2020-01-reverse-hiv-latency-important-scientific.html 4.In animal models, a 'shocking' step toward a potential HIV cure https://medicalxpress.com/news/2020-01-animal-potential-hiv.html