Nat commun: new research reveals new mechanism of immune system detection and response to HIV infection

January 26, 2020 / Biovalley BIOON / - -- since the introduction of antiretroviral drugs (Art) against HIV infection in 1996, scientists have been keen to find a way to cure the disease Although art drugs can make people living with HIV live a normal and healthy life, they must take drugs for life A small proportion of HIV can remain dormant in immune cells for several years, so if a patient stops taking art drugs, the dormant HIV will leave the dormant state and infect the patient again Now, as the first people to start art therapy move into middle age or old age, doctors are seeing side effects of inflammation caused by lower circulating HIV levels This is another reason to develop a cure for the disease This is from the center for molecular inflammation research, University of science and technology, Norway In a new study, researchers from the Norwegian University of science and technology, the University of Oslo and Tsinghua University in China found that the immune system detects and responds to HIV infection in a previously unknown way, which may improve the chances of curing the disease Relevant research results were recently published in the Journal of nature communications, and the title of the paper is "sensing of HIV-1 by tlr8 activates human T cells and reverses latency" Background when HIV enters the body, it will infect the immune system to resist its immune cells, namely CD4 helper T cells (CD4 T cells) Once these T cells are infected, they cannot protect the body from other diseases or infections Therefore, the disease caused by HIV infection is called acquired immunodeficiency syndrome (AIDS) In the case of a full-scale outbreak of AIDS, patients have few T cells and will die of any infection or disease that does not affect people with a healthy immune system "Today, we have drugs to prevent HIV from self replicating, and CD4 T cells can be regenerated," said Hani Zakaria me å s, a postdoctoral researcher at the center for molecular inflammation research at the Norwegian University of science and technology and co lead author of the paper You can live a completely healthy life, but you have to take medicine all your life, because the day you stop treatment, HIV will rebound " If you stop taking art drugs, HIV will rebound because the virus hides its genetic material in dormant T T T T cells This means that there is always the possibility of more viruses and serious damage These pools of HIV virus stimulate the world to find ways to drive the virus out of the cells it harbors Me å s said that if the latent HIV virus can be driven out, and then it can be killed by the immune system or drugs, then the patient's body will not have HIV, and can be cured "We need to activate the virus so that it can start replicating, so that the cells that are potentially infected with HIV are visible to the immune system This is the current search for a cure for it We just need to activate the cells that are potentially infected with HIV, so we can kill them, and we also provide drugs to protect the cells from infection, given that more viruses will be produced during activation " He said a clinical trial in the UK called the river study tried this method, but last year's report showed that the trial was unsuccessful There are different variants of HIV, but not all variants can infect all helper T cells equally In order to infect cells, the virus must have a specific ligand that recognizes and binds to specific receptors on the target cells When a helper T cell does not have a receptor that matches the ligand on the HIV virus, it cannot actively infect the T cell Instead, the virus can be trapped in cells called endosomes The researchers studied the capture of uninfected helper T cells in the body by HIV Me å s said that these uninfected helper T cells respond to HIV in the body by destroying its contents In the past, scientists believed that this specific pathway - HIV is trapped in the body of helper T cells, which destroy the contents of the body - is a dead end of HIV infection After all, helper T cells are not actually infected, and their insides destroy the virus But now, the researchers have found an immune response that was not previously described, which is caused by the destruction of HIV in the body It may be the key to developing "shock and kill" latent HIV virus The researchers found that when HIV in vivo is destroyed, some of its genetic material is exposed to T cells, which in turn activates a molecule called tlr8 This leads to cytokine production, which leads to inflammation in the body One surprising reason is that T cells are part of the "adaptive" immune system, and over time they become familiar with and respond to infectious substances There is also a little-known "innate" immune system that provides general immune protection by identifying and responding to common viral or bacterial fragments Tlr8 is part of the body's innate immune system T cells are part of the adaptive immune system Generally speaking, the two systems are considered to be two separate branches "In this new study, we found that a receptor associated with the innate system actually exists and functions in the adaptive immune system," said me å s Markus Haug, CO lead author of the paper and a researcher at the molecular inflammation research center of the Norwegian University of science and technology, said that inflammation caused by cytokines awakened previously dormant T T T T T T cells containing HIV genetic material "T cells detect HIV and produce cytokines that act on cells infected with the virus and make them produce more viruses," Haug said These latent helper T cells produce viruses, and these active virus producing T cells will produce more viruses " In other words, tlr8 signaling and cytokine induced inflammation drive HIV out of these latent cells, which can destroy the virus The destruction of HIV in the body and its associated inflammation may also be why patients who have been treated with art for decades now begin to suffer from inflammatory diseases more common in people over the age of decades These inflammatory diseases include dementia, cardiovascular disease, metabolic syndrome and cancer unrelated to HIV Me å s said that the destruction mechanism of HIV in vivo may release enough genetic material to activate the innate immune receptor of T cells, which can lead to inflammation In addition, the findings do offer hope, said co-author Jan Kristian dam å s of the University of Trondheim hospital in Norway "Today, we have very effective drugs to suppress HIV," said dam å s However, we are unable to eradicate the virus, and it will reactivate from the HIV library a few weeks after the patient stops taking the drug If we can eradicate these libraries, then we can find a cure for HIV infection " This breakthrough paper by me å s and Haug brings new insights into reversing the underlying mechanism of HIV, and their discovery of tlr8 as an important receptor for HIV in T cells clearly represents a potential new target for HIV treatment In addition, their findings may also represent significant progress in vaccine development, because tlr8 ligands may be used as vaccine adjuvants, thus shaping the type of T-cell response induced by HIV vaccines (BIOON Com) reference: 1 Hany zekaria me å s et al Sensing of HIV-1 by tlr8 activates human T cells and reverses latency Nature communications, 2020, doi:10.1038/s41467-019-13837-4 2.A newly discovered mechanism allows the immune system to detect and respond to HIV https://medicalxpress.com/news/2020-01-newly-mechanism-immune-hiv.html