End of 2019: Interpretation of 2019 HIV heavyweight study

November 30, 2019 / bioun / - -- human immunodeficiency virus (HIV), or AIDS (acquired immunodeficiency syndrome) virus, is a virus that causes human immune system defects In 1983, HIV was first discovered in the United States It is a lentivirus that infects cells of the human immune system It is a retrovirus HIV destroys the T lymphocyte of human body, and then blocks the process of cellular immunity and humoral immunity, leading to the paralysis of the immune system, which leads to the spread of various diseases in human body, and ultimately leads to AIDS Due to the rapid variation of HIV, it is difficult to produce specific vaccine, so far there is no effective treatment, which poses a great threat to human health Since the 1980s, the AIDS epidemic has claimed more than 34 million lives According to the statistics of the World Health Organization (who), it is estimated that 36.9 million people around the world were infected with HIV in 2017, of which only 59% of those infected with HIV received antiretroviral therapy (Art) So far, HIV is still one of the biggest public health challenges in the world, so it is urgent to study the function of HIV in depth to help researchers develop new therapies that can effectively combat the disease In order to prevent the massive replication of virus from damaging the immune system, people with HIV need to take art every day or even for life Although it has been proved that art can effectively inhibit the onset of AIDS, but such drugs are expensive, time-consuming and labor-consuming and have serious side effects There is an urgent need to find a cure for HIV infection So far, only one "Berlin patient", Timothy Ray Brown, has been reported in the world to be completely cured of HIV In 2007, brown received CCR5 △ 32 / CCR5 △ 32 hematopoietic stem cell transplantation in a German hospital to treat leukemia After that, his HIV virus disappeared completely and he became the first AIDS patient who was "cured" in the world In March 2019, a male patient known as "London patient" who had received a bone marrow transplant from an HIV resistant patient did not show signs of HIV infection for nearly 19 months He is likely to become the second known successful HIV removal patient in the world In the coming 2019, scientists have made great progress in the risk factors, pathogenesis, detection and treatment of HIV Let's take a look at the major findings in this field in this year 1 Nature: heavyweight! To reveal the mechanism of HIV recruitment of ftsj3 to evade innate immune recognition of host nature, published online: 09 January 2019, DOI: 10.1038/s41586-018-0841-4 in mammals, 2 '- O-methylation of RNA is a molecular feature of innate immune system of cells to distinguish endogenous messenger RNA (mRNA) and exogenous mRNA However, the molecular function of RNA 2 '- O-methylation has not been fully understood In a new study, French researchers purified TAR RNA binding protein (TRBP), its interaction partner, and identified a TRBP complex containing ftsj3 independent of Dicer, in which ftsj3 is presumed to be a 2 '- O-methyltransferase In vitro and in vivo experiments showed that ftsj3 was a 2 '- O-methyltransferase which was recruited to HIV RNA through TRBP Using ribomethseq analysis, the researchers identified 2 '- O-methylation, which is mainly dependent on ftsj3, at specific sites in the HIV genome From CDC / C goldsmith, P feorino, e L Palmer, W R McManus CC by 0 The HIV-1 virus produced in ftsj3 knockdown cells (referring to the cells whose ftsj3 gene expression is inhibited) shows reduced 2 '- O-methylation and triggers the expression of type 1 interferon in human dendritic cells via RNA sensing protein MDA The induced expression of IFN - α and IFN - β leads to the decrease of HIV expression 2 Science: to reveal the mechanism of HIV nanoparticle immunogen targeting germinal center mediated by innate immune system, science, 08 February 2019, doi:10.1126/science.aat9120 In a new study, researchers from multiple research institutions, such as Massachusetts Institute of technology, compared the fate of two different highly glycosylated HIV antigens - a small protein derived from gp120 and a large stable envelope protein (Env) trimer - after primary immunization in the form of protein nanoparticles or free form Unlike monomer antigens, nanoparticles are rapidly transported to the follicular dendritic cell (FDC) network, and then aggregated in the germinal center in the form of complement dependent, mannose binding lectin (MBL) and immunoglobulin glycan dependent forms The researchers then found that in mice lacking MBL, failure of immunogens to locate in FDC cells or disaccharization of immunogens significantly affected antibody response These results are of particular concern in the context of HIV vaccine development, because in the existing HIV vaccine development process, the tight HIV envelope "glycan shield" is often seen as an obstacle to achieve efficient antibody response 3 Cell: Gao Guangxia research group of Chinese Academy of Sciences has revealed a new anti-virus factor inhibiting HIV-1 programmed-1 ribosome migration mechanism cell, 24 January 2019, DOI: 10.1016/j.cell.2018.12.030 HIV-1 uses programmed-1 ribosome frameshifting, - 1prf) to generate the necessary gag and gag pol for virus replication Gao Guangxia of the Institute of biophysics of the Chinese Academy of Sciences and his team reported a new host antiviral factor that inhibits-1prf, which they call shiftless Picture from cell, DOI: 10.1016/j.cell.2018.12.030 In order to explore the mechanism of shiftless, Gao Guangxia's research group analyzed the interaction between shiftless and - 1 PRF RNA and ribosome in translation, and the latter two are the two key factors in the process of - 1 PRF Shiftless and the latter two interact Based on this result, they speculated that the simultaneous binding of shiftless with ribosome and - 1 PRF RNA in translation might cause ribosome to fall into a nonproductive state, thus stagnating on - 1 PRF RNA Stagnant ribosomes should be rescued through quality control mechanisms, leading to premature translation termination 4 Nature: the new method can accurately measure the size of latent HIV virus library, which is 10 to 100 times more accurate than the existing method nature, 07 February 2019, Doi: 10.1038/s41586-019-0898-8 in a new study, Dr Robert siliciano and his colleagues from Johns Hopkins University School of medicine in the United States developed a new genetic technology, which can quickly and accurately calculate the inactive HIV form in patients' cells, which is a key part of evaluating the effectiveness of new HIV therapy This form of latent HIV is integrated into the genome of cells, and even if patients receive successful treatment, they can persist, which hinders efforts to cure HIV infection According to their report, previous tools overestimated the number of latent HIV by 10 to 100 times, which may have masked a significant decline in experimental therapies Although it may still be a long way to go to cure HIV, at least for now, the new research has made important progress The relevant research results were published in the nature Journal on February 7, 2019 The title of the paper is "a quantitative approach for measuring the reservoir of late HIV-1 viruses" Using two fluorescent probes of different colors, the siliciano team designed a PCR reaction that could distinguish defective HIV templates from complete HIV templates The HIV DNA regions targeted by these probes are prone to mutations that can lead to HIV template defects, and the color readout value can indicate whether HIV genetic instructions are defective This means that scientists can use the new technology to assess whether an intervention, such as an experimental drug or drug mixture, is affecting a potentially life-threatening genetic library of HIV 5 Nature: heavyweight! Scientists have found the world's second fully cured HIV infected people! Nature, Published online: 05 March 2019, Doi: 10.1038/s41586-019-1027-4 ten years after the world's first AIDS patient was successfully cured, researchers from Cambridge University and other institutions recently found that a man known as "London patient" has not been infected with HIV for nearly 19 months, and relevant research results were published in the international journal Nature The London HIV infected man who received a bone marrow transplant from an HIV resistant patient is likely to become the second known successful HIV removal patient in the world, the researchers said The picture is from CDC / who / UNAIDS / avert.org/amfar.org/merckmanuals.com In 2003, the British man was infected with HIV However, in 2012, he was diagnosed with Hodgkin's lymphoma In 2016, the man's condition became worse Then doctors decided to carry out a matching transplant operation for him to treat Hodgkin's lymphoma The donor of the transplant carried a gene mutation called CCR5 Delta 32, which can help the body effectively offset the disease To fight HIV, after receiving a stem cell transplant from a donor, HIV in the British man's body was eliminated The researchers believe that the cure of Berlin patients is not an abnormal phenomenon At present, they do not know whether CCR5 resistance is the key to the elimination of HIV in patients Few people carry CCR5 gene mutation Only 10% of European people carry CCR5 gene mutation In addition, hematopoietic stem cell transplantation still needs matching Therefore, it is still necessary for ordinary people to rely on CCR5 gene mutation to completely cure the disease Further study 6 NEJM: great progress! The new antibody can inhibit HIV for up to 4 months! And will not produce drug resistance! NEJM, 18 April 2019, DOI: 10.1056/nejmoa1802264 according to a new study, for patients undergoing a short-term suspension of antiretroviral therapy (Art) program, regular injection of an antibody that blocks the binding site of HIV in human immune cells can inhibit HIV levels for up to four months The results of phase II open clinical studies show that the antibody, ub-421, is safe and will not induce HIV with antibody resistance Twenty nine volunteers with good HIV control stopped their daily oral antiretroviral treatment regimen after the first injection or a week Fourteen study participants received regular injections of ub-421 eight times a week, and 15 participants received high doses of ub-421 eight times a week At the end of the treatment period of 8 or 16 weeks, all volunteers resumed their previous art protocol and were evaluated at a follow-up visit after 8 weeks In addition to a participant who stopped the study due to a mild rash, both groups of volunteers maintained good HIV suppression throughout the treatment period without antiretroviral treatment (plasma HIV RNA levels below 20 copies / ml) 7 Ebiomedicine: it's heavy! For the first time in history, programmed MDC1 cells were used to force latent HIV to emerge and kill it, ebiomedicine, published online: 02 April 2019, Doi: 10.1016/j.ebiom.2019.03.077 in their first attempt to cure HIV infection, researchers from the Graduate School of public health at the University of Pittsburgh in the United States reported that they had developed an integrated immunotherapy method that could not only hide HIV in the immune system