Cell Rep: new research shows that it's important to suppress HIV from the beginning

December 17, 2019 / Biovalley BIOON / - -- 1.7 million people around the world are infected with human immunodeficiency virus (HIV) every year They are forced to receive antiretroviral drugs (Art) for life or face the risk of fatal AIDS Of the 37.9 million people living with HIV around the world, 22.3 million have access to art treatment, bringing their life expectancy close to normal Unfortunately, however, these drugs can only stop there: they can't reach HIV cells that have been dormant for many years In addition, their potential long-term adverse reactions are still unknown Picture from cell reports, 2019, DOI: 10.1016/j.celrep.2019.10.094 Nevertheless, HIV research is steadily moving forward to help a large number of people living with HIV HIV labs around the world are trying to break the virus's "secrets" and find its weaknesses in order to prevent or cure the virus infection In a new study, é ric A Cohen, tram NQ Pham and colleagues from the clinical research institute in Montreal, Canada, identified a way to prevent HIV infection at an early stage The related research results were recently published in the Journal of cell reports, and the title of the paper is "Flt3L mediated expansion of plasmacytoid exotic cells supplies HIV infection in humanized mice" Vulnerable window: key first days Cohen said: "contrary to popular belief, HIV is not so easy to spread We are looking at the virus's fragile window, the moment when it can be weakened or attacked during infection We focus on the very early stages of the virus's invasion " HIV does not spread to the whole body immediately when it is transmitted It must initially proliferate locally, mainly in reproductive organs Only after this initial local proliferation can the virus spread This local proliferation provides a very short and fragile window before the virus can effectively establish systemic infection The immune response is like an armed struggle: the enemy penetrates, the body defends itself The virus is the invader, and the white blood cells are the soldiers who try to hold the fort White blood cells are equipped with their own "infantry units": lymphocytes, phagocytes, granulocytes, etc Phagocyte population has a more special kind of infantry unit, which is called plasma like dendritic cell (PDC) These smaller round cells patrol the body and specialize in pathogen detection and antiviral response coordination In other words, they are whistleblowers, through which the entire defense process can be initiated When they detect a threat, they change shape and produce a protuberance called a dendrite "Most importantly, they start to produce a lot of interferon, a protein that triggers other cells to enter an infection resistant state," Cohen explained As the name suggests, HIV targets the immune system preferentially: it attacks and weakens the body's own defenses, making infected people sensitive to the slightest infection Once HIV enters, the virus clears PDC cells and prevents them from alerting "The virus doesn't seem to kill them directly, but the way they disappear is still unknown," Pham said The loss of PDC cells at the site of infection and throughout the body helps to establish infection " "Given the impact of HIV on PDC cells, we would like to know what happens if we improve the level and function of PDC cells before and during infection," said Cohen, a humanized mouse model against HIV infection To test this, the researchers used a special protein called FLT3 receptor ligands to stimulate the production of PDC cells in human derived mouse bone marrow The rodents are genetically engineered to carry the human immune system in place of their own Therefore, in the infected humanized mice, HIV behaves the same as in the human host The application of this specific protein can maintain high levels of PDC cells in these mice, and produce some surprising results: 1) the initial number of infected mice has been reduced; 2) the time required to detect the virus in the blood has been prolonged; 3) the viral load in the blood (also known as viremia) has been greatly reduced "We observed a 100 fold reduction in viremia," Pham said In other words, maintaining a high level of PDC cells can inhibit the initial infection " Significance for vaccine design this groundbreaking study also showed that the injection of FLT3 receptor ligands not only increased the abundance of PDC cells, but also enhanced their ability to detect HIV and produce interferon after detection of the virus Of course, HIV infection is usually not noticed, which is a little too late when viremia is detected In this context, Cohen and Pham's findings are important for HIV prevention and potential cure "These new findings are crucial for the design of HIV vaccines, after all, the basic goal of such vaccines is to teach the immune system self-defense by introducing a weakened virus into the immune system," Cohen said We are now focusing on PDC cells to control the seeding and proliferation of the virus in the early stages of infection " (BIOON Com) reference: 1 Tram n.q Pham et al Flt3L mediated expansion of plasma deterministic cells supplies HIV infection in humanized rice Cell reports, 2019, DOI: 10.1016/j.cellep.2019.10.094 2 HIV: beyond the energy from the start https://mediaexpress.com/news/2019-11-hiv-overwheel-energy.html