TOP 25 Interpretating of Marvelous Researches on HIV !

There are many marvelous researches on HIV in 2017, and here is an overall summary of the top 25.

1.PLoS Pathog: the HIV reservoir is expected to be clear via JAK inhibitors.
doi: 10.1371 / journal.ppat.1006740

According to a new study, a class of anti-inflammatory drugs that have been approved by the FDA for the treatment of rheumatoid arthritis may be able to “clear” the immune cell bank of the virus with which the HIV-infected persons infected.

When culturing immune cells from HIV-infected individuals, researchers found that tofacitinib and ruxolitinib, two anti-inflammatory drugs, can block the infected cells from producing HIV and thus spreading it to cells nearby, and clear this virus gene pool.

Relevant findings, titled “Novel mechanisms to inhibit HIV reservoir seeding using JAK inhibitors”, were published in PLoS Pathogens on December 21, 2017.

The new study involved 37 HIV-infected people, and all of them control the virus in their bodies by taking antiretroviral drugs. The size of the residual HIV reservoir in these infected individuals, namely, the number of immune cells that HIV integrates into the genome, correlates with enzyme activity of JAK in these immune cells. This suggests that blocking the JAK enzyme may actually result in depletion of the HIV reservoir. Laboratory experiments confirm that JAK inhibitors prevent HIV from spreading to nearby healthy cells.


2. PNAS: New research makes it possible to kill HIV.
doi: 10.1073 / pnas.1712033114

Now, in a new study, researchers from Loyola University in Chicago discovered a protein that helps the virus migrate in a rather quick way. They found that absence of this protein could make the virus lodge in the cytoplasm, where it can be detected by cellular virus defense systems.
Relevant finding, titled “Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection.”, was published online in the PNAS on November 22, 2017.

HIV-1 must go cross the cytoplasm into the nucleus after it invades the cell. Once inside the nucleus, HIV-1 controls cells and self-proliferates. But it’s not easy to cross the cytoplasm. Cytoplasm consists of liquids rich in proteins and mitochondria and other structures, which stops the virus spreading here owing to the size of the virus.

For HIV-1, it goes straight rapidly to reach the nucleus through tubular tracks called microtubules, and attaches itself to a molecular motor called dynein, migrating along microtubules like a train on a track. Campbell and colleagues found that it was bicaudal D2 (BICD2), a protein, that works as a ticket for getting HIV-1 on board. After HIV-1 binds to BICD2, motor proteins are recruited. Kinetic proteins then migrate HIV-1 into the nucleus.

3.Nature: When against HIV and other viral infections, the spelling order of basic group plays an important role.
doi: 10.1038 / nature24039

A new study, conducted by researchers from Rockefeller University in the US, found a key similarity between our healthy genes and many viral genes, that a way of spelling the genetic code could make the virus escape cellular defense.

Paul Bieniasz, a professor at Rockefeller University who led the study, noted the study was initially designed to understand how the viral genome affects the infectivity of HIV.

Relevant finding, titled “CG dinucleotide suppression enables antiviral targeting non-self RNA.”, was published in the Nature, Oct. 5, 2017.

Humans are not the only one who lack CG sequences, so do the common HIV and many other viruses, out of different reasons. The researchers speculated that there may be a cell monitoring system to identify and destroy CG sequences, thus preventing the virus infection. They use new gene editing techniques to find proteins that could play such a defensive role. Consequently, in human cells, an anti-viral protein called ZAP (Zinc-finger Antiviral Protein) was found to recognize DNA molecules with many CG sequences. When ZAP binds itself to these CG sequences, it will label those sequences as intruders and destroy them immediately.

This result offers new insight into what causes the loss of CG sequences among HIV and other viruses as time flies. These viruses are also likely to adapt to mammalian defense mechanisms and remove their CG sequences after evolving, thus avoiding surveillance from ZAP.

4.PNAS: Breakthrough! Scientists shed new light on the molecular mechanisms by which HIV intercepts host cells to proliferate the virus.
doi: 10.1073 / pnas.1706600114

Recently, a study, published in the Proceedings of the National Academy of Sciences, conducted by researchers from the University of Chicago pointed out that they found a previous unknown detail about HIV through computer simulation techniques. The detail is how HIV coerces host cells into spreading viruses to other cells, which is expected to help researchers develop new therapies to treat HIV infection according to the related studies.

Scientists are well aware of the process of budding that mainly involves the protein complex called Gag in HIV, but they are not clear about the specific molecular process involved. Researchers has known the final assembly structure, but all the details still remain secret.

Researcher Gregory Voth said that we ccould hardly get images of the protein complex at the molecular level only by using imaging technology. So in this study, we constructed a computer modeling technique to simulate the mode of action of the Gag protein complex, which offered a clearer observation of the construction of molecular process with an adjusting freedom from the researchers. Later, the observed structure was confirmed by laboratory experiments.

The researchers constructed a model that lacked a key part of the Gag protein complex, and they later adjusted it for clearly seeing how the proteins used the host cell’s basic structures to trigger budding process, which in turn, assembled key proteins. This study illustrates the power of using modern computer technology to model virus activity. The researchers are looking forward to the achilles heel of HIV. Once they get it,it may be possible to develop new drugs to block the accumulation of Gag protein complex, thus effectively curbing the proliferation of HIV. Their next plan is to conduct an in-depth study of the structure of Gag proteins after HIV starts budding.

5.Science: New approach to producing Bryostin with an improvement up to 10,000 times in yield, which is promising to treat cancer and HIV.
doi: 10.1126 / science.aan7969;
doi: 10.1126 / science.aao5346

A new study from Stanford University in the US, found a simpler and more efficient way to make such a compound in increasing demand in the lab. Their newly synthesized drug can sufficiently support continuing clinical trials to test its efficacy as a cancer immunotherapy, Alzheimer’s treatment and HIV treatment. Relevant finding, titled “Scalable synthesis of bryostatin 1 and analogs, adjuvant leads against latent HIV.”, was published in Science on 13 October 2017.

The story of bryozoans started in 1968 when a marine biologist working in the Gulf of Mexico collected a large amount of marine life and sent them to the National Cancer Institute for analysis. As one of the creatures, Bugula neritina is a pest known for its ability to contaminate the marine environment and is expected to become an anti-cancer agent. Fifteen years later, scientists reported the structure of the active ingredient, and named it as brymbus 1 referring to a common name of the marine animal, brown bryozoan. Unfortunately, brynidin 1 is hard to get. These NCI scientists only successfully extracted 18g of it on the basis of 14 tons of bugula neritina.

With decades of experience in the research of bryostatin analogues, Wender Lab has developed, over a two-year effort, a less-complex synthetic method. There are only 29 steps in this method with a yield of 4.8%.  The synthetic efficiency, tens of thousands of times higher than that of bugula neritina, is significantly simpler and more efficient than the previous one.

6.Cell Rep: Scientists firstly confirmed the “hiding place” of HIV virus, making HIV elimination possible!
doi: 10.1016 / j.celrep.2017.09.081

For decades of seeking HIV virus, scientists from the Westmead Institute of Medicine in Sydney, have for the first time confirmed that, infectious HIV in immune memory was hidden in humans Immune memory T cells, evading the detection of the immune system.

A team led by Sarah Palmer, an associate professor at the University of Sydney, has developed a groundbreaking genetic sequencing method for the detection of the AIDS virus. This new generation of tests shows that HIV is hidden in the body’s immune memory cells, making it avoid being detected in the immune system.

Professor Palmer explained that only a very small proportion of the HIV, nearly 5%, is genetically intact. However, it is exactly this small proportion of the virus hidden in effector memory cells that prevents the immune system from completely destroying the virus and removing it from the body.

7. Science: A three-pronged antibody is expected to stop HIV infection!
doi: 10.1126 / science.aan8630

In a new study, U.S. researchers reported that a three-pronged antibody (trispecific antibody) made in their lab was better than its synthetic raw material, mono natural antibody for helping monkeys escape from the infection of two human monkey chimeric immunodeficiency virus (SHIV) strains.
Relevant finding, titled “Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques.”, was published online in Science on September 20, 2017.

This trispecific antibody, developed by researchers from the National Institutes of Health (NIH) and Sanofi, a French pharmaceutical company, can block more infected cells with HIV strain than single native antibodies in a stranger way in terms of lab performance.This new broadly neutralizing antibodies work by combining itself to three different key points of the HIV.

Currently, these researchers are planning an early clinical trial of this trispecific antibody among healthy people and people with HIV positive, hoping to make it a long-term method of preventing and treating HIV. By combining with three different HIV sites, this virus should be harder to evade the trispecific antibody compared with mono natural antibody.


8.Science sub-issue: HIV infection can be prevented by injecting an antibody mixture!
doi: 10.1126 / scitranslmed.aao4235

According to a promising animal study, a combination of antibody may be the key point to stop the spread of HIV. A new study, conducted by researchers from the National Institutes of Health (NIH), the Beth Israel Deaconess Medical Center, the Lagen Institute, the Los Alamos National Laboratory and the Scripps Research Institute, showed a combination of antibody injection made a group of laboratory monkeys completely protected from HIV infection. A mixture of two HIV antibodies, PGT121 and PGDM1400, was inoculated among these monkeys in a way of combinatorial antibody injection.

Relevant finding, titled “Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail.”, was published in Science Translational Medicine, on September 20, 2017.

However, there are downsides to this strategy. Given that these antibodies are injected into the body rather than naturally produced by the immune system, a regular antibody injection is a must for maintaining people’s ability to fight HIV. This strategy focuses on the broadly neutralizing HIV antibodies, a class of antibodies that bind to the HIV virus to prevent it from invading the target immune cells.


9.Mol Cell:  Reactivate latent HIV with anti-cancer drug JQ1.
doi: 10.1016 / j.molcel.2017.07.025

HIV carriers must take three or more different drugs daily during the rest of their lives. Unfortunately, the side effects of this therapeutic schedule range from mild dizziness to life-threatening liver damage. However, HIV hidden in their cells can spontaneously reappear if they stop taking these medications.

In fact, the latent HIV, which can hide in cells for years, is exactly a key obstacle to the cure. Scientists are exploring two main strategies to solve this problem: reactivating and eliminating this latent HIV (called “shock and kill”) or finding a way to permanently silence it.

In response to both strategies, researchers from the University of California, San Francisco and Icahn County Mount Sinai, recently studied drugs that undermine this potential and could eventually be used to treat HIV-infected individuals. And they found a new drug, called JQ1, can reactivate latent HIV. JQ1 is currently in early clinical trials of human cancers.
Relevant finding, titled “The Short Isoform of BRD4 Promotes HIV-1 Latency by Engaging Repressive SWI / SNF Chromatin-Remodeling Complexes.”, was published on September 21, 2017.

Melanie Ott, author of the paper, memeber of the Glaxo Institute at the University of California, San Francisco, said: ” Frustration makes our findings. At first, we knew that JQ1 targeted a protein called BRD4, but our experiment did not prove it. We then started to look at different forms of this protein and unexpectedly discovered that a shorter form of this protein was the key to silence HIV. ”

By identifying a new role for this shorter form of BRD4, the Ott team could eventually explain the mechanism of controlling HIV latency. They confirmed that JQ1 targeted and removed this shorter form of BRD4, allowing the virus to replicate itself.



10.JCI Insight: mTOR inhibitors inhibit HIV replication in your gut!
doi: 10.1172 / jci.insight.93230

A new study from the University of Montreal Hospital Research Center (CRCHUM) in Canada found a way to delay viral replication in the gastrointestinal tract of HIV-infected individuals. This progress may lead to the development of new therapeutic strategies to complement antiretroviral therapy (ART), improve control of viral replication in HIV-infected individuals, and prevent complications associated with chronic infections.
Relevant finding, titled “HIV-1 selectively targets gut-homing CCR6 + CD4 + T cells via mTOR-dependent mechanisms.”, was published online in JCI Insight on August 3, 2017.

ART, used to treat HIV-infected individuals, reduces the viral load in the blood to undetectable levels and effectively prevents the conversion from HIV infection to acquired immunodeficiency syndrome (AIDS). Ancula explained, “Although antiretroviral agents are effective, HIV lurks in cells of particular immune system (i.e., CD4 T cells) that contain the virus, forming HIV reservoirs in a variety of peripheral tissues, especially the stomach Gut. In the HIV reservoir, some of HIV continues to replicate, bringing harmful inflammation in the gut. Therefore, we want to make it possible to ​​limit viral replication and resistance to inflammation at various levels. ”

CD4 T cells migrate from the bloodstream into the gut by virtue of molecule markers on their surface, a molecule marker called CCR6, which is like the “zip code” of these cells for directing themselves into the gut. Previously, these researchers have demonstrated that CD4 T cells expressing the CCR6 molecule are a preferred target of HIV infection in vitro and are an HIV reservoir in subjects undergoing ART treatment.

The Ancuta team and the Jean-Pierre Routy team from the McGill University Institute of Health Center in Canada jointly found that CCR6-expressing CD4 T cells in the colon also contain large amounts of another molecule called mTOR, which is an important metabolic regulator, by using blood and sigmoid colon biopsies from HIV-infected patients with ART treatment.

By using existing drugs to interfere with the activity of mTOR in vitro experiments, researchers were able to significantly reduce HIV replication in CD4 T cells that were undetectable in terms of viral load from HIV-infected individuals.



11.PLoS Pathog: Synthetic molecule SUW133 is expected to kill latent HIV in the body.
doi: 10.1371 / journal.ppat.1006575

Researchers from the National Institutes of Health (NIH), the University of California, Los Angeles, and Stanford University designed a synthetic molecule that could reactivate latent human immunodeficiency virus (HIV, commonly known as the AIDS virus) in mice and make some of the infected cells die. Relevant finding, titled “In vivo activation of latent HIV with a synthetic bryostatin analog effects both latent cell” kick “and” kill “in strategy for virus eradication.”, was published in PLoS Pathogens on September 21, 2017.

To solve this problem, Matthew Marsden, Jerome Zack from UCLA and Paul Wender and his team from Stanford University devised a synthetic molecule that mimicked activity of brynx-1 activity and perhaps even enhanced its function. SUW133, in this new study, is one of the more promising brymbus-1 analogues synthesized by researchers.

These researchers first confirmed that SUW133, like brymbus-1, can activate latent HIV in cells from HIV-infected individuals. Subsequently, they tested SUW133 in a mouse specie commonly used in HIV research, whose immune system after modification was similar to human immune system.
Molecular analysis revealed that in these mice, SUW133 stimulated HIV protein expression in cells infection by latent HIV. Almost 25% of these cells died within 24 hours. These mice showed better tolerance to SUW133 compared to brynchin-1.

These results prove SUW133 has the potential to be used in “activate and kill” therapeutic strategies against HIV. However, further research is needed to unlock its potential and answer some questions, such as whether a greater percentage of cells can be killed over a longer period of time or multiple doses; whether a similar effect may be observed in the human body; what is the possible long-term effect of SUW133.


12.EBioMedicine: Vorinostat makes latent HIV easily cleared!
doi: 10.1016 / j.ebiom.2017.07.019

HIV can hide in the human body in a latent state, which pose great challenge to the treatment of 40 million people infected with HIV. Now, researchers from the University of North Carolina at Chapel Hill in the United States confirmed that Vorinostat could reverse this latency, making static CD4 T cells express HIV antigens.They developed an assay to detect the production of HIV antigens, which includes an immune effector that clears this virus.

Relevant finding, titled “Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV) Vulnerable to Clearance by CD8 T Cells.”, was published in EBioMedicine on July 28, 2017.

Vorinostat offers a window of vulnerability for clearing the HIV virus pool by triggering the production of HIV antigens. The researchers have developed a latency clearance assay (LCA) to measure HIV antigen activity triggered by Vorinostat. This assay also includes clearing the immunopotentiators expressed by this viral antigen cells.

Dr. Julia Sung, the first author of this paper, an assistant professor of medicine at the Department of Infectious Diseases at the University of North Carolina at Chapel Hill, said: “The ability to measure a latent reversal agent that induces the production of HIV antigens is technically challenging. Through the latency clearance assay, we detected that Vorinostat, a latent reversal agent in clinical trials, induces the expression of HIV protein at recognizable levels on the surface of the cells, allowing the subsequent clearance of infected cells.


13.Nature: Rapid generation of HIV broadly neutralizing antibodies via cows.
doi: 10.1038 / nature23301

Scientists have long sought an HIV vaccine that causes broadly neutralizing antibodies, (bNAbs), which is believed to be the key to preventing the infection of many strains of HIV. However, this proved to be a difficult task because only about 20% of HIV-infected patients produce these antibodies. A new study proves dairy cows may be qualified for this job.
Relevant finding, titled “Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows.”, was published in Nature on July 20, 2017.

In the past few years, HIV broadly neutralizing antibodies was defined to be a larger protein that is difficult to control. At the same time, scientists also found that dairy cows’ antibodies tend to be similarly larger and more difficult to control.

Devin Sok, lead author and director of antibody discovery and development from the International AIDS Vaccine Initiative, said: “This is the result of a collaborative effort among veterinarians, antibody scientists of dairy cow, and HIV scientists.  We just discuss and talk together for solving this relatively simple question.”

Sok and his colleagues are sure that HIV broadly neutralizing antibody can be triggered among four dairy cows who have been immunized with a protein immunogen that mimics HIV-like Envelopes (BG505 SOSIP) in terms of antigenicity.Two months after the first immunization, they took blood samples from these cows, isolated the antibodies and demonstrated in vitro that these antibodies effectively blocked the infection of multiple HIV strains.

14. JCI: Interval administration of Vorinostat reverses HIV latency.
doi: 10.1172 / JCI92684

In an effort to develop therapies for healing nearly 40 million people with HIV positive worldwide, an ongoing test is going like exposing the latent HIV reservoir for their self-disappearing.

A new study, from the University of North Carolina at Chapel Hill in the United States, confirmed that interval dosing of Vorinostat can reverse HIV latency and show a good tolerance in HIV-infected individuals. However, although vorinostat makes latent HIV more easily detectable, it does not clear the infection, which means that further progress is needed for cure.
Relevant finding, titled “Interval dosing with the HDAC inhibitor vorinostat effective reverses HIV latency.”, was published in Clinical Investigation on July 17, 2017.

The researchers studied Vorinostat among 16 infected patients whose viral loads were controlled by standard antiviral therapy. Vorinostat is administered at 48-hour or 72-hour intervals. They found that HIV could be more easily detected in latent infected CD4 + T cells when vorinostat was administered every three days, even the viral load in the blood was maintained.


15.Nature: A first capture of transition state structure of the HIV envelope protein!
doi: 10.1038 / nature23010

Human immunodeficiency virus (HIV) currently infects about 37 million people all over the world. HIV has a key protein complex called the Env trimer, whose complex structure, to a large extent, stops the development of a vaccine that controls and blocks HIV infection.

A new study, from the Scripps Research Institute (TSRI), Shaq Institute of Biology, and Will Medical School of Cornell University, firstly shows structure figure of the Env protein complex at a close-up of the atomic level. This map reveals the complex conformational changes happens in different parts of the Env trimer, which occur only before the virus fuses with the plasma membrane of an immune cell under normal conditions. These findings may provide potential new targets for designing HIV vaccines.

Relevant research, titled “Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.”, was published in Nature on July 12, 2017.

HIV infection happens necessarily after Env’s binding with two proteins on the outer surface of T cells: first binding goes with a membrane receptor called CD4 and the second is a co-receptor called CXCR4 or CCR5.

In this new study, the researchers constructed a protein that includes a modified Env, genetically engineered to increase its stability, which is bound to CD4 and 17b. As a human antibody, 17b, similar to CXCR4 / CCR5, is used as a surrogate for these co-receptors. This trimeric complex images itself by being embedded in a thin layer of ice and then placed in a cryo-EM for imaging.

Jesper Pallesen, a co-author of the paper and senior researcher at TSRI, said: “Detailed two-dimensional pictures come from the electron beams that are scattered by protein atoms. And we have almost 2,000 pictures, each containing thousands of frozen Env complex in random orientations. We create a high-resolution 3D structure through aligning them by calculating.”

The researchers also conducted a second antibody replacement experiment to get the clearest structural map of Env whose structure is changeable so far. Ward said, “Given that Env is a metastable fusion machine, it has long been known that it must be a malleable structure.”

By using b12, a similarly shaped antibody to CD4, to replace CD4, researchers confirmed that Env could be distorted to a kind of “partial-closed” state, where b12 can go in but CD4 cannot, in addition to the “closed” state where the CD4 binding site was hidden and an “open” state where the CD4 is ready to be bound.


16.Science: Anti-HIV drug failure may result from some vaginal bacteria!

doi: 10.1126 / science.aai9383;
doi: 10.1126 / science.aan6103

In the world, the HIV virus infects over 1 million women annually. A new study, from Canada, the United States, South Africa, and Sweden, found that some types of vaginal bacteria could interfere with the drug gels designed to stop the risk of HIV infection.
Relevant finding, titled “Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women.”, was published in Science on June 2, 2017.

These findings are based on a 2010 study of how tenofovir, a microbicide drug in vaginal gels for women in South Africa, is used to assess HIV transmission blocking.

The drug proved to be successful in preventing high-risk HIV infection in men, but disappointing in women. The researchers found that women infected with HIV tend to have a predominant bacterium called Gardnerella vaginalis that “may rapidly metabolise and degrade the active form of the drug.” Gardnerella vaginalis is related to a condition known as bacterial vaginosis (BV). Bacterial vaginosis is confirmed to increase the risk of HIV infection as it increases inflammation, damages the vaginal wall and impairs wound healing. Women from sub-Saharan Africa have a higher prevalence of bacterial vaginosis.

Susan Tuddenham and Khalil G. Ghanem, from Johns Hopkins University in the US, write that given that bacterial vaginosis recurs in nearly 60% of women after one-year treatment, it is still not clear whether changing this group of microorganisms might allow tenofovir gel to perform better.


17.JCI: Revealing the mechanism that the HIV virus persists despite the treatment.

doi: 10.1172 / JCI93289

Most cells in the human body have a finite lifespan and usually die after days or weeks. However, cells infected by HIV-1 can successfully persist for decades. Current HIV therapies are very effective at inhibiting this virus but cannot eliminate it. Once the treatment is stopped, the relapse comes rapidly.
A new study, conducted by Dr. Mathias Lichterfeld and Dr. Guinevere Lee from Infectious Diseases at Brigham and Women’s Hospital in the United States and their team, unveiled the mechanism that cells infected with HIV-1 still continue despite antiviral treatment.
Relevant finding, titled “Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4 + T cells.”, was first published in Clinical Investigation on June 19, 2017.

By using a new viral sequencing method to track HIV viral infections in different subtypes of CD4 T cells, researchers found that a significant number of HIV-infected cells contained sequences that were identical concerning the entire full-length viral sequence.

Indeed, a single cell cluster containing these same sequences was observed in nearly 60% of memory CD4 T cells, the major target cell for HIV invasion. These data suggest that cells carrying the same viral sequences are all from a specific CD4 T cell and such T cells are likely to have been infected with HIV prior to antiviral treatment. The cells spread when they divide and expand the population of HIV-infected cells. This T cell transmits viral genetic material into its daughter cells through a process called “clonal proliferation” when in cell division. With this mechanism, a single HIV-infected cell can multiply up to a million times by dividing it 10 to 20 times.

Lee said, “This study shows that HIV effectively uses the normal proliferation of human cells to expand and spread the HIV virus genome.”

18. Mol Ther: Scientists successfully use CRISPR / Cas9 to eliminate HIV-1 infection in live animals!

doi: 10.1016 / j.ymthe.2017.03.012

A completely cure for HIV infection remains impossible as the virus can hide itself in the HIV reservoir.

Recently, a report, published in the international magazine Molecular Therapy, jointly written by researchers from Temple University and University of Pittsburgh, indicated that ablating HIV DNA from the genome of live animals could eliminate HIV-induced post-infection. And this finding was proved by the
three different animal models, including humans derived mouse model (a mouse model transplanted into human immune cells), a mouse model infected with a virus, and the like.

In the article, researchers first discovered that CRISPR / Cas9, “Gene Monster”, can completely turn off the replication of HIV-1 and eliminate the virus in the infected cells of the animal’s body.

This study is based on a proof-of-concept study in 2016. In this previous test, researchers incorporated DNA from HIV-1 into the genome of each tissue in an animal model body by using transgenic rat and mouse models. As a result, it can remove targeting fragments of HIV- of the tissue genomes 1 in most experimental animals.

Researcher Hu said,” The research is very significant. We not only confirmed the previous studies, but also improved the efficiency of gene editing strategies. Meanwhile we found the gene editing strategy effective in another two mouse models. One showed an acute infection of rat cells and the other showed a chronic or potential infection in human cells.”


19. Nature: CD32a, a marker for HIV reservoir of CD4 T cell.

doi: 10.1038 / nature21710

French researchers found a way to pinpoint the unidentified white blood cells that provide hiding places for the HIV in people who take anti-HIV drugs.In order to observe and someday neutralize HIV, these cells from “HIV reservoir” have long been the supreme goal of eradicating AIDS and the HIV virus causes it.

There is currently no cure for HIV infection and infected people have to take antiviral drugs for life. This is because a small percentage of white blood cells called CD4 T cells, provide a hiding place for the HIV virus so that it can emerge and spread again after the treatment is stopped even after decades’ treatment.

Researchers successfully observed the protein CD32a present on the surface of HIV-infected cells from the HIV reservoir when testing the HIV-infected blood. And this protein is deficient in healthy CD4 T cells.

An HIV-infected person has about 200 billion CD4 T cells, but only one out of every million CD4 T cells can be HIV reservoir. Among 5 liters of adult blood, 2% of the human CD4 T cells (about 4 billion) express this protein, which means that there are about 80 million CD4 T cells in 100 microliters of blood samples. And about 80 are virus banks from all those CD4 T cells.

However, one important question is whether CD32a is actively involved in keeping this virus hidden in CD4 T cells. If so, it may be an attractive target for developing drugs that block this process of concealment.

Douglas Richman, an AIDS researcher at the University of California San Diego in the United States, who did not participate in the study, cautions that although this study is described as “potentially significant,” CD32a is found only in about half of the CD4 T-cell virus bank. To eradicate latent HIV, there is a great need to target the remaining CD4 T-cell virus bank that does not contain this marker.


20. Three studies prove that synthetic HIV envelope mimics are expected to induce broad-spectrum neutralization HIV antibody!

doi: 10.1126 / scitranslmed.aai7514;
doi: 10.1126 / scitranslmed.aai7521;
doi: 10.1016 / j.celrep.2017.02.003

In two new studies, researchers from the United States, South Africa and Malawi described production pathways of protective HIV antibody and a synthetic HIV envelope mimic that has the potential to induce the production of these antibodies by vaccination.

“The goal of the HIV-1 vaccine is to induce widespread neutralizing antibody.” said Dr. Barton F. Haynes, co-author of the paper and director of the Duke Human Vaccine Institute (DHVI) in the US Duke Human Vaccine Institute.

“The strategy is to find a way to develop a small part of the envelope structure of HIV that require antibodies’ recognition. For now, we have proved this strategy is possible. ”

In the first study, Haynes and his colleagues (including Dr. Mattia Bonsignori from DHVI) spent five years tracking a series of events that made broadly neutralizing antibodies, bNAbs, occur in an HIV-infected individual. They found that this infected person’s response to the immune system was that the broadly neutralizing antibodies in his body was induced by an unusual collaboration between different B-cell lineages. The production process of this antibody also involves a rare genetic change that is crucial for protective antibody activity.

In the second study, a team of researchers, from the Sloan Kettering Cancer Memorial in the United States under the leadership of Dr. Samuel Danishefsky, used the blueprint to construct a synthetic molecule, which mimics the target site involved in infection on the HIV envelope. They also tested whether it could induce similar antibody production after inoculating this molecule to non-human primates.

As an immunogen, this molecule mimics an exact region (or binding site) in this virus. Immune attack works when some broadly neutralizing antibodies are bound to this area. This synthetic immunogen accurately mimics this binding site and, can induce the production of the antibody that targets this key site in non-human primate vaccination studies,

The team reported that the synthetic molecular mimics induced antibody production at this site more rapidly than we observed in this HIV-infected person.

A third study from DHVI confirmed that monkeys can be vaccinated with HIV envelopes, producing antibodies that target HIV envelope glycoconjugates.

Under the leadership of Dr. Kevin O. Saunders, these researchers used HIV envelopes to immunize monkeys for three years and found that these monkeys produced an antibody that targets broadly neutralizing antibody binding sites (containing sugar molecules) of the HIV envelope after such prolonged immunization.

Haynes said “All three studies support the idea of ​​designing vaccine candidates that mimic key areas of the HIV envelope. The goal, is to assemble all the HIV components that trigger the production of these protective antibodies into one vaccine that can be tested in the body.

21. Nature: Early antibody immunotherapy is expected to induce long-term anti-HIV immune response.
doi: 10.1038 / nature21435

Now, a new study from the National Institutes of Health and Rockefeller University suggests that immediate treatment with two anti-HIV antibodies after HIV infection allows the immune system to effectively control the virus and stop it from relapse over a long period of time. Relevant research was published in Nature on March 13, 2017.

Michel Nussenzweig, co-author of the paper and director of the Molecular Immunology Laboratory at Rockefeller University and researcher in Howard Hughes Medical Institute, said: “This therapy induces a potent anti-HIV immune response that allows the host to control the infection. Like some cancer immunotherapy, it depends on the natural defense mechanisms of the immune system.”

This study was conducted in monkeys by simian-human immunodeficiency virus (SHIV). Although this SHIV infection does not accurately model human HIV infection, these findings suggest that one should develop an immunotherapy to treat this viral infection by controlling HIV and increasing the immune response that may be able to control the HIV infection in the patient.

The two antibody drugs used in this study, 3BNC117 and 10-1074, belong to broadly neutralizing antibodies, which were discovered in the study of “elite controllers” by Nussenzweig labs. The elite controller’s immune system features excellent resistance to HIV. Both antibodies block HIV’s damaging effects in different ways with individually binding to different sites in HIV.

At first, give the SHIV virus injections to the 13 monkeys and then add three intravenous injections of both antibodies within two weeks. This treatment suppresses the virus, allowing it to drop below or near the limit of detection. And its efficacy can last up to six months. After the two antibodies were cleared inside, 12 monkeys underwent a virus rebounding.
But then, after 5 to 22 months, something notable happened: six of the monkeys spontaneously regained control of the virus again. Their virus levels again felll to undetectable levels, again maintaining their inhibition of this virus for 5 to 13 months. After receiving these antibody injections, these six monkeys also maintained a healthy level of vital immune cells.

In addition, the other four monkeys did not regain full control of the virus once again, but their treatment showed promising responses: CD4+ T cells in their bodies, a vital immune cell, were maintained in an extremely low viral load and health levels after two to three years of infection Of CD4 + T cells, In all, 10 of these 13 monkeys benefited from this antibody immunotherapy.

Nussenzweig and his colleagues also studied which aspects of the immune system helped these monkeys prevent the virus from running back. The six elite monkeys were injected with an anti-CD8β monoclonal antibody that targets the depletion of cytotoxic T cells (ie, CD8 + T cells).
Injecting this antibody immediately increased the SHIV load in the blood of these monkeys and decreased cytotoxic T-cell levels, indicating that these cells play a crucial role in preventing SHIV replication following the injection of this therapeutic antibody.

22. JCI: URMC-099 to extend the efficacy of HIV drugs!

doi: 10.1172 / JCI90025

A drug, developed by the University of Rochester Medical Center, initiates a defense against HIV by its own cells, thereby prolonging the efficacy of various HIV drugs.

This discovery represents a significant step toward the goal of developing drugs that will work long-term with one or two doses a year, and at present, patients must take daily HIV medication.

Relevant finding, titled “Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs.”, was published in Clinical Investigation on January 30, 2017.

The drug, called URMC-099, was developed by Dr. Harris A. Gelbard, a scientist at the University of Rochester Medical Center. URMC-099 initiates a process called autophagy when used in combination with two commonly used versions of anti-HIV drugs (also known as antiretroviral drugs).

Under normal circumstances, autophagy allows cells to clear intracellular “junk”, such as invading viruses. When infected with HIV, the virus prevents cells from initiating autophagy, which is one of the many tricks it uses to survive. When autophagy is started, the cells are able to digest any virus that survives from the antiretroviral treatment, leaving the cells free from virus infection for an extended period of time.


23. Science Ezine: A combination of three antibodies may make HIV nowhere to run!
doi: 10.1126 / scitranslmed.aal2144

Most HIV-infected people eventually will get trapped in Acquired Immune Deficiency Syndrome (AIDS) if they do not receive any antiretroviral therapies.

Because the virus changes and evolves for escaping from human’s control. But a small group of infected people (known as elite controllers) have an immune system defeats the virus. Broadly neutralizing antibodies are the secret, which are able to inhibit a variety of HIV strains.

Now, in a new study, Michel Nussenzweig, director of the Molecular Immunology Laboratory at Rockefeller University in the United States, and his team confirmed that the combination of these three antibodies completely suppressed the virus in mice infected with HIV. Relevant findings were published in Science Translational Medicine on January 18, 2017.

The immune system of an elite controller produces new broadly neutralizing antibodies, as well as cytotoxic T cells. Put simply, their immune cells can recognize and destroy infected cells and prevent them from spreading.

The patient’s immune response to HIV infection generated the antibodies used in this study. He worked with the Nussenzweig team for 10 years, providing his blood for their research. He was infected with HIV at least 30 years ago and has produced three different types of broadly neutralizing antibodies. These three antibodies bind to three different sites on the surface of the virus.

As to his antibodies, it is noteworthy that they seem to complement each other’s activity, completely inhibiting HIV.The researchers injected the three antibodies (called BG18, NC37 and BG1) into HIV-infected mice that had previously been genetically engineered to make their immune system act more like the human immune system. They found that after three weeks of injection, the three antibodies did not allow the virus to be detected in two-thirds of mice.

24. Science Issue: One of the most potent HIV neutralizing antibodies to date has been found!
doi: 10.1126 / sciimmunol.aal2200

Researchers in the United States, South Africa and Malawi declared that they have constructed the most potent antibodies against HIV. In a paper published in Science Immunology on January 27, 2017, they described how they can use the natural antibodies that are uniquely resistant to HIV to construct these new antibodies, and What does it mean in terms of HIV vaccine developing?

The study began with the discovery of a patient who created an antibody that can neutralize many different HIV strains. This is crucial given the way in which research on vaccines is structured. It is not enough to find such an antibody in just one patient; the researchers looked back on the history and found out its production in a particular human being — the host’s immune system worked by means of B-cell mutation in a few years.

In the meantime, researchers also looked at plasma from the same patient and identified another useful antibody, an antibody that has been linked to an antibody they had previously discovered, and both antibodies were a variant of an antibody called DH511.

Next, the researchers obtained fragments of each antibody from the two antibodies they obtained, and then used the fragments to construct a new antibody until they thought it was the most potent combination of antibody fragments.

Tests indicate that they bring important benefits because this antibody has been shown to neutralize 206 of the 209 HIV strains worldwide. They note that this antibody is so effective due to its unique binding properties that make it very similar to the outer membrane of the HIV virus, allowing it to block important aspects of the HIV virus’s life cycle.

25.Science: Scientists successfully decode key structure of HIV virus!
doi: 10.1126 / science.aah5163

Scientists at the Salk Institute in the United States recently analyzed the atomic structure of a key part of the HIV virus. The key structure, called intasome, helps HIV integrate into human host DNA and relevant researches were published in Science.

In the new study, researchers used a single-particle cryo-electron microscope, helping scientists capture pictures of larger and more complex dynamic molecules. They added a special protein to the virus intasome to promote the solubility of the intasome in glycerol and added some salt ions to prevent the protein from agglomerating.

All retroviral intasome have core structural elements to perform integration functions. The researchers compared the core components of HIV intasome with PFV and found some differences. They noted that although the differences were small, they can be very important for drug development and understanding of drug resistance mechanisms.

To the surprise of the researchers, HIV intasome are more complex than other retroviruses. It is known that the core of an HIV intasome consists of four parts. But new research finds that there are many more components there. Research suggests that more complex intasomes can better HIV integrating itself into the host genome.

The researchers said that the complexity of HIV intasome suggested how nature can shape the evolution of retroviruses. The HIV virus can do things that other viruses cannot do, such as entering the nucleus through an active transporter without waiting for cell division. Researchers make an analogy: HIV is like a luxury car, while other retroviruses are economical cars. All of them are cars, but the HIV intasome has been upgraded to do different things.

Researchers speculate that HIV integrates in a variety of ways. At present, the current study focuses on the assembly of assembled DNA on the host DNA. In the future, the integration of the host genome with the drug-integrated structure will be studied.


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