[in depth inventory] breakthrough research progress in the field of AIDS in 2015

At present, there are 35 million people living with HIV all over the world, and most people who need AIDS drugs have no conditions for treatment In 2001, there were 3.4 million new HIV cases in the world, while in 2013, the number of new cases decreased by 38% to 2.1 million; 75% of the infected people were mainly concentrated in 15 countries, such as sub Saharan Africa, Nigeria, South Africa and Uganda, which accounted for 48% of the total number of new HIV infections In the past few years, the number of AIDS deaths has decreased by 20% According to the UNAIDS report, human beings are expected to end the AIDS epidemic after 2015 and "end AIDS by 2030" In order to achieve this desire, governments and organizations all over the world need to work together, of course, there is no lack of scientists who are constantly engaged in AIDS research December 1, 2015 is the 28th "World AIDS Day" The theme of this year's activity is still "getting to zero" and the subtitle is "working together to fight AIDS, share responsibilities and share the future" Then, the editor will take stock of the breakthrough research in the field of AIDS research in 2015 【1】 PNAs: the molecular mechanism of HIV-1 capsid decomposition helps the development of new AIDS therapy imagine that when a suitcase is knocked open on a bumpy journey, the clothes in the suitcase will fall on the ground; and the similar embarrassing things are like your suitcase cannot be opened when it is time to open The above metaphor shows the importance of HIV-1 capsid for HIV-1 Capsid is a protective "capsule" to protect HIV-1 Once the virus enters the body cells, it must decompose and release the viral nucleic acid at the right place and at the right time Recently, in a research paper published in the international journal PNAs, researchers from the center for Health Sciences of the University of Texas in the United States said through research that up to now, there is still a debate in the scientific community about when the capsid of HIV-1 virus will decompose in the infected cells In this study, we have revealed how an HIV-1 inhibitor named pf74 and the host protein cpsf6 Combined with the small grooves on the surface of virus capsid to inhibit the decomposition of capsid, and then to inhibit the infection and transmission of virus Dr Ivanov said: 'we believe that a clear analysis of this process may help to develop new targeted therapies for HIV-1 infection In this paper, we use X-ray crystallography technology to clearly observe the three-dimensional structure of the protein cpsf6 that binds to the HIV-1 capsid 【2】 Nature: HIV is also picky Recently, the famous international journal Nature published a new research result of Italian scientists online They found that human immunodeficiency virus type 1 (HIV-1) tends to integrate in the nuclear membrane area close to the nuclear pore of the host cell nucleus, and select genes that are actively transcribed in this area for integration This study may provide important clues for the study of the host genome integration of HIV-1 Human immunodeficiency virus (HIV) is a kind of lentivirus that infects the cells of human immune system It belongs to retrovirus Up to now, there is no effective treatment method to completely treat this fatal infectious disease HIV can destroy human immunity, leading to immune system loss of resistance, leading to a variety of diseases and cancer, and ultimately the patient's immune system collapse, access to AIDS For HIV and other retroviruses, the integration of viral DNA into host DNA is a key step in their life cycle Long term studies have shown that human immunodeficiency virus type I (HIV-1) tends to integrate into the gene regions with active transcription in host cells However, it is still unclear why the virus only selects some specific genes for integration among all genes with active transcription in host cells 【3】 Nat Immunol: HIV storage pool is an obstacle to cure AIDS Recently, antiretroviral therapy (Art) has been proved to be life-saving therapy for people living with HIV; however, for most people living with HIV, this therapy must be used for life, and then comes problems in personal life, economy and health The main goal of our research is to find a way to cure AIDS, which can not only remove the virus from the body of HIV infected people, but also inhibit the virus level of HIV infected people, and maintain a very low level of virus content without daily art treatment In an article from a new perspective, Anthony S Fauci, director of the National Institute of allergy and infectious diseases (NIAID), and his colleagues describe how HIV persists in the human body and why treating it is so difficult In addition, in the absence of daily art treatment, the current treatment strategy is to eliminate or control the virus, including making CD4+ T cells produce resistance to HIV and improve the host's immunity against infection The authors say that it is important to better understand how the virus has a long-term storage pool in the body and the impact of treatment interventions on the development of successful treatment strategies for long-term control of HIV infection 【4】 Science: scientists have developed a new type of AIDS vaccine Since 1984, when HIV was the cause of AIDS, more than 100 AIDS vaccines have entered the clinical trial stage, but they all failed Robert Gallo published four articles in science when he was working in the National Cancer Research Institute He used strict data to demonstrate the relationship between HIV and this global epidemic disease Since then, efforts on HIV vaccine development have continued Now, however, Professor Gallo, who heads the National Institute of human viruses (IHV), has always looked at the whole thing as a spectator Gallo's research team is working with protectus biosciences to develop a new type of HIV vaccine with a protection period of up to 15 years Protectus Biosciences is a biotechnology company separated from IHV In the phase I clinical trial, they recruited 60 volunteers to test the safety and immune response of the vaccine The vaccine is called "full length single chain" "That's a bad name," Gallo said directly The vaccine includes a class of HIV surface protein gp120, which binds to CD4 receptors on the surface of lymphocytes and enables the virus to "trickle" into the second receptor CCR5 When both receptors are combined, HIV can infect cells successfully IHV vaccine is mainly used to induce tine to produce specific antibodies against gp120, block the binding ability of the virus and CCR5, and thus interrupt the virus infection The development of the vaccine was led by George Lewis of IHV 【5】 Cell: a major breakthrough in HIV research: virus self-control At present, the biggest obstacle to the treatment of individual HIV infection is that the virus can be hidden in many cell banks composed of dormant immune cells, and scientists generally believe that HIV will not replicate in these dormant immune cells, because the virus must rely on active organelles to survive Recently, in two articles published in the international famous journal Cell, from the United States Researchers from the Institute of allergy and infectious diseases found that HIV can control whether the virus replicates by itself, and the incubation period can provide the basis for the survival of the virus Relevant research may reveal why the HIV treatment strategy that awakens latent immune cells will eventually fail In the first study, the researchers said that when the cell transition from infection stage to other stages, HIV will be inhibited in an active state By using computer model technology, the researchers found that HIV protein named Tat can be used as a controller of virus switch, and by controlling the level of Tat protein, the state of the virus will continue to change; conversely, modifying the state of the host cell will affect the disease There was no effect on the incubation period In order to confirm the researchers' findings, they used the synthetic biological technology to effectively separate the virus and the cell, so as to directly control the Tat protein The results showed that changing the level of Tat protein can effectively turn on or off the activity of the virus, but activating or releasing the activity of the host cell has no effect on the replication of the virus 【6】 PNAs: new bottle opener molecules lead HIV virus out of the hole Recently, in a research paper published in the international journal PNAs, researchers from the University of Montreal and other places have identified a new way through research, which can use a "bottle opener" to drive HIV to expose its sensitive "parts", so that the immune cells kill the infected cells The study opens a new way to fight HIV infection and provides new clues for the development of new vaccines to inhibit the spread of HIV Researcher Andres Finzi said: 'we found that there are naturally produced antibodies in HIV-1 infected individuals, which can potentially kill the infected cells We just need to add a molecular switch, and give a little "impetus" to make it work, and this molecular switch can play the role of a bottle opener, to promote the exposure of the virus to the parts recognized by the antibodies, so as to stimulate immunity Infected cells attack infected cells In early studies, researchers found that when Nef and Vpu proteins are inactivated by gene mutation, the serum of HIV-1 patients can promote the elimination of infected cells These two proteins are very important for HIV-1 However, in reality, HIV-1, the virus that causes most of the infections, still has the two proteins mentioned above as the guard of the virus, so what should scientists do ? The researchers said that by adding a molecular switch jp-iii-48 to the cell surface of the patient's body, it can impersonate CD4 protein, which is located on the surface of T-lymphocytes and can promote the immune cells to be infected by HIV 【7】 Cell: anti HIV-1 innate immune adjuvant receptor newly found that natural immune response plays an important role in the transmission and pathogenesis of HIV-1, and HIV-1 itself has evolved a series of immune responses that escape from ISG (IFN stimulated genes) Recently, some studies have found that there may be one or more signaling pathways in natural immune cells to recognize the characteristic molecular substances of HIV-1 and cause downstream immune responses, such as IFN expression As we all know, dendritic cell (DC) is an important barrier of natural immunity, and also an important link between natural immunity and acquired immunity Due to the existence of a Phosphohydrolase protein called samhd1 in human DC, it can degrade the nucleic acids in the cell, so that DC itself is very resistant to HIV-1 Previous studies have successfully induced HIV-1 infection in DC by introducing a kind of VPX protein secreted by HIV-2 / SIV (which can promote the ubiquitination and hydrolysis of samhd1) This experiment proves that this condition can not only promote the proliferation of HIV-1 in the cell, but also promote the cell to secrete IFN For the production of IFN, previous studies have reported many related signal pathways, and one of the most important is the expression of IFN caused by the recognition of DNA by cgamp synthetase Although previous studies have found that cgamp can participate in the natural immune response of HIV-1, it is unclear whether there is a direct interaction between HIV-1-related PAMP and cgamp Recently, the sumit K Chanda research group from Sanford Burnham Institute of medicine in the United States published in the journal Cell