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Simulations have led to the fabrication of a polymer-DNA gel that could be used in tissue regeneration and robotics.
Scientists in Japan have made a tuneable, elastic and temperature-sensitive gel by using complementary DNA strands to connect star-shaped polymer molecules together. The gel, and the method used to develop it, could lead to advances in tissue regeneration, drug delivery and soft robotics. Xiang Li at Hokkaido University led the team of researchers who reported their findings in the journal Polymer Science.
Scientists have long been looking for better ways to develop gels that can be used in a variety of applications, including in the fields of medicine and engineering. Ideally, such gels need to be predictable in their behaviour, self-healing and durable enough for the rigorous jobs they are intended for.
“Gels are made by using bonds to link polymer molecules together,” explains Li. “When the bonds are connected, the material is more solid, and when they break in response to stress, the material turns to liquid.”
Owing to their high biocompatibility, water solubility and temperature sensitivity, DNA strands would be highly suitable for linking polymer molecules by taking advantage of their ability to form complementary bonds. However, scientists have so far found it difficult to use DNA links to develop homogeneous gels with on-demand elastic properties.
Looking to solve this problem, Li and his colleagues used software programs to simulate the formation of different DNA sequences and their complementary strands, and to determine how these double strands respond to changes in temperature. Their aim was to identify complementary DNA sequences that would only disconnect above 63°C in order to ensure a potential gel’s stability in the human body.
Based on the software simulations, they chose a pair of complementary DNA sequences to link four-armed molecules of polyethylene glycol (PEG). They prepared the gel by dissolving DNA strands and PEG separately in buffer solutions before mixing them in a test tube immersed in a hot water bath that was then cooled to ambient temperature. Finally, they conducted a series of experiments and analyses to evaluate the resulting gel’s properties.
The gel performed as predicted by the simulations, remaining elastic, self-repairing and solid until its melting temperature of 63°C over multiple testing cycles. The experiments also showed that the PEG molecules were homogeneously linked together by the DNA double strands and that liquid formation happened when the strands separated.
“Our findings suggest that we will be able to fabricate DNA gels with on-demand viscoelastic properties by making use of already available data on DNA thermodynamics and kinetics,” says Li. “The aim will be to improve the understanding and applications of this class of gel.”
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Our immune systems have the potential to find and destroy cancer cells. But cancer cells can be clever and develop tricks to evade the immune system. Cold Spring Harbor Laboratory Professor Douglas Fearon and his former postdoc ZhiKai Wang found one such trick. Cancer cells weave a deactivating signal into a protective coat of armor that excludes T cells that would otherwise kill them. This immune deactivation pathway offers a promising new therapeutic approach for pancreatic, breast, and colorectal cancers.
T cells patrol the body looking for cancers and pathogens. If they and/or their immune system teammates find an intruder, the T cells are mobilized to attack. Wang, currently a research fellow at the University of Science and Technology of China in Hefei, discovered this mobilization was disabled by a combination of three proteins woven into a protective coating surrounding cancer cells: a signal that usually attracts T cells called CXCL12, a filament called KRT19, and a protein that fuses the former proteins together called TGM2.
The scientists used genetic editing to turn off the production of KRT19 or TGM2 in mouse pancreatic tumors. Without KRT19 or TGM2, the cancer cells lost the CXCL12-KRT19 protection and T cells were able to infiltrate and attack. The pancreatic tumors shrank or disappeared.
Why did this coat of proteins repel T cells from the tumors? Wang says, “It is kind of counterintuitive because CXCL12 is a chemokine (chemical attractant) that attracts immune cells. But we found that CXCL12 is in an unusually high concentration on the surface of the cancer cells, where it does the opposite by making T cells immobile.” CXCL12 usually does its work as a single protein. But at high concentrations on the surface of cancer cells, the protein is in a complex with KRT19 and forms a branch-like network. T cell movement was reduced dramatically by this network.
The study was published in the Proceedings of the National Academies of Sciences. In a previous small clinical study of pancreatic cancer patients, Fearon and collaborators showed that the drug plerixafor (a CXCL12 receptor blocker) increased the infiltration of T cells into patients’ pancreatic tumor tissues. The current study now shows why this immunotherapeutic effect occurs. Fearon and Wang hope CXCL12 and KRT19 will provide new therapeutic targets that boost the immune system’s chances of killing off cancer cells.
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Materials provided by Cold Spring Harbor Laboratory. Original written by Luis Sandoval. Note: Content may be edited for style and length.

Cholera, a diarrheal disease caused by the highly transmissible bacteria Vibrio cholerae, kills tens of thousands of people each year worldwide. Current vaccines last only 2-5 years, and they don’t work very well in young children. Now, researchers reporting in ACS Infectious Diseases have developed a new type of cholera vaccine consisting of polysaccharides displayed on virus-like particles. The vaccine generated long-lasting antibody responses against V. cholerae in mice.
Current cholera vaccines contain killed or weakened V. cholerae bacteria and are administered orally. They offer the lowest level and duration of protection in young children, who are commonly affected by cholera in endemic countries. The immune system produces antibodies against the O-specific polysaccharide (OSP) on the surface of V. cholerae, but this polysaccharide in isolation does not generate a strong, long-lasting immune response. Peng Xu, Edward Ryan, Xuefei Huang and colleagues wondered if attaching OSP to virus-like particles could induce stronger, longer-lasting immunity.
So the researchers developed a method to efficiently link multiple copies of OSP to Qβ, a virus-like particle that infects bacteria. The modified virus-like particles were recognized by antibodies in blood taken from recovering cholera patients, but not from patients with typhoid, another bacterial disease. Next, the team immunized mice with Qβ-OSP, observing that three doses caused a strong antibody response that persisted at least 265 days after the first dose. The immunized mice had antibodies that recognized the OSP from the natural lipopolysaccharide of V. cholerae. When the researchers mixed serum antibodies from the mice with other immune system proteins that kill bacteria and with live V. cholerae, antibodies from two of the five mice triggered more bacterial death than those from mice immunized with Qβ alone. The virus-like particle could mimic natural bacteria by presenting multiple copies of OSP on its surface, the researchers say, and it warrants further evaluation as a next-generation cholera vaccine.
The authors acknowledge funding from the National Institutes of Health, the Fogarty International Center and Michigan State University. Xuefei Huang is the founder of Iaso Therapeutics Inc.
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First announced by the World Health Organization on Nov. 26, 2021, the SARS-CoV-2 omicron variant spread rapidly around the world, becoming the dominant variant in the U.S. and elsewhere. Now, researchers report in ACS Infectious Diseases and the Journal of Chemical Information and Modeling that omicron and other variants are evolving increased infectivity and antibody escape, according to an artificial intelligence (AI) model. Therefore, new vaccines and antibody therapies are desperately needed, the researchers say.
Understanding how SARS-CoV-2 evolves is essential to predicting vaccine breakthrough and designing mutation-proof vaccines and monoclonal antibody treatments. In a recent study in ACS Infectious Diseases, Guo-Wei Wei and colleagues analyzed almost 1.5 million SARS-CoV-2 genome sequences taken from people with COVID-19. They identified 683 unique mutations in the receptor binding domain (RBD), the region of the SARS-CoV-2 spike protein that attaches to the human ACE2 receptor on the surface of human cells. Then, they used an AI model to predict how these mutations affect binding strength of the RBD to ACE2 and to 130 antibody structures, including several monoclonal antibodies used as therapies. The team found that mutations to strengthen infectivity are the driving force for viral evolution, whereas in highly vaccinated populations, mutations that allow the virus to escape vaccines become dominant. The researchers also predicted that certain combinations of mutations have a high likelihood of massive spread.
In another study in the Journal of Chemical Information and Modeling, Wei and colleagues took a deep dive into the omicron variant’s infectivity, vaccine breakthrough and antibody resistance. They used their AI model to analyze how the variant’s unusually high number of mutations on the spike protein affect RBD binding to ACE2 and antibodies. Their results indicated that omicron is over 10 times more infectious than the original coronavirus and 2.8 times more infectious than the delta variant. In addition, omicron is 14 times more likely than delta to escape current vaccines, and it is predicted to compromise the efficacy of several monoclonal antibody therapies. Many of these predictions have been verified by emerging experimental results, stressing the importance of developing a new generation of vaccines and monoclonal antibodies that won’t be easily affected by viral mutations, the researchers say.
The authors acknowledge funding from the National Institutes of Health, the National Science Foundation, NASA, the Michigan Economic Development Corporation, the Michigan State University Foundation, Bristol-Myers Squibb and Pfizer.
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Could he be having a stroke — or was it something more unusual?“OK, I give up,” said the 74-year-old man. “I’ll go to the hospital.” His wife of 46 years gave an inner sigh of relief. Her husband was stubborn, a seventh-​generation Mainer, not given to complaining. But a few weeks earlier, she noticed that he was parking his tractor next to the back porch so he could get on it without pulling himself up. Then he needed help getting out of his big chair. Now he could barely walk. It happened so suddenly it scared her.She eased the car right next to the porch. He needed both hands on the railing to get down, grunting with each step. His legs moved awkwardly, as if they had somehow forgotten what to do.At the LincolnHealth-Miles Campus Hospital in nearby Damariscotta, it was clear to the E.R. doctors that the patient wasn’t weak but ataxic, lacking not strength but coordination. Virtually every movement the body makes requires several muscles working together — a collaboration that occurs in the cerebellum. The uncertain and awkward way the patient moved made doctors at LincolnHealth worry that something — maybe a stroke, maybe a tumor — had injured that part of the brain. But two CT scans and an M.R.I. were unrevealing.When his doctors weren’t sure what to do next, the patient decided it was time to go home. His wife was supportive but worried. How could she help him get around? He was a big guy and outweighed her by 50 pounds. And they still needed to figure out what was wrong with him. Couldn’t they try another hospital? Maybe, he said, but first he wanted to go home. So that’s where she took him. Once there, it took only a day for the man to recognize, again, that he couldn’t just tough it out at home. There was another hospital, a larger one a couple of towns over in Brunswick: Mid Coast Hospital. His wife was happy to take him there. Those few steps he took from porch to car, supported by his wife, were the last he would take for weeks.Photo illustration by Ina JangDown the Wrong TubeHe couldn’t walk, the older man told Dr. Roople Unia, the neurologist on call that day. He could barely stand up, he continued. And that wasn’t the only thing: He was seeing double. And he had a terrible cough. Of course, at 74, he had a bunch of medical problems — diabetes, high blood pressure, some heart disease, even gout. But nothing had laid him this low before. His tanned round face reddened as he surrendered to a violent cough.Unia suspected that his swallow was as uncoordinated as his walk. The esophagus (the swallowing tube) is right next to the trachea (the breathing tube). Normally the epiglottis, a leaf-shaped flap located at the base of the throat, folds over the trachea as we swallow to prevent the food meant for the esophagus from going down the wrong tube. The cough, she suspected, was his body’s last-ditch effort to keep food, liquids and his own saliva out of his lungs.Unia knew from the records from the first hospital visit that this wasn’t a brain tumor or stroke. Could it be a vitamin B12 deficiency? Loss of this key nutrient can cause a wide variety of neurological symptoms — usually difficulty walking and a loss of feeling in the hands and feet, sometimes double vision and trouble swallowing as well. And it’s common — seen in up to 15 percent of those over 60. Vitamin B1 and E deficiencies, while less common, can also cause these kinds of neurological symptoms.Something else that can affect the brain and nerves are autoimmune diseases. These disorders occur when the immune system gears up to take on some kind of invader, and the antibodies generated to protect the body attack it instead. Some of these autoimmune diseases are associated with cancers. These paraneoplastic syndromes, as they are called, are a rare consequence of the immune system’s attacking cancer but can cause devastating injuries to the nervous system as well as other parts of the body.An Unusual VariantBut highest on Unia’s list of suspects was an unusual version of Guillain-Barré syndrome (G.B.S.) known as the Miller Fisher variant. G.B.S. is also an autoimmune disorder, usually triggered by an infection. Antibodies created to fight the infection mistakenly attack the nerves that control movement, usually starting with the legs and ascending up the body. In the Miller Fisher variant of G.B.S., the disease attacks the nerves controlling the muscles of the head and neck as well as those of the feet and legs, causing double vision and difficulty swallowing.Unia ordered the blood test that looks for this version of G.B.S. But the results could take weeks. In the meantime, the neurologist decided to treat him even without this proof. Treatment involves suppressing the wayward immune system — first with steroids and then, if needed, with intravenous immunoglobulin (IVIg), an infusion of antibodies that block the destructive ones of G.B.S.New Developments in Cancer ResearchCard 1 of 6Progress in the field.

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesAnalysis of more than 30 bottles of wine has found two glasses could be enough to reach the recommended daily sugar limit for adults.Research by Alcohol Health Alliance UK found some bottles had up to 59g of sugar – more than a glazed doughnut.An independent laboratory analysed bottles of red, white, rosé, fruit and sparkling wine from popular UK brands.None of the bottles featured nutritional information on labels as this is currently not required by law.Calorie content was only displayed on a fifth of the bottles analysed by the lab. Campaigners are calling for change, to better inform wine drinkers about how many calories and how much sugar they are consuming.The NHS recommends adults consume a maximum of 30g of “free sugars” per day, which includes sugar in fruit juices and smoothies, or sugar added to food or drink. Analysis shows that it’s possible to reach an adult’s daily sugar limit by drinking two medium-sized glasses of some wines.Image source, Getty ImagesIt also found lower-strength wines were among those containing the most sugar, meaning they were not necessarily a healthy choice, despite their lower alcohol content.In the UK, alcoholic drinks are required to display volume and strength in units of alcohol by volume (ABV).’Hidden sugar’ in pre-mixed gin and cocktail drinksSugar reduction in food well below target of 20%Labelling must also identify any common allergens, but there are no requirements for ingredients, health warnings or nutritional value as found on many other food and drink food products. A YouGov survey of more than 12,000 people last year found that 61% wanted calorie information on wine labels – and more than 50% of those surveyed wanted the amount of sugar listed. In 2020, the UK government held a consultation on whether calories should be listed on alcoholic drinks – but there was no consultation on whether sugar content should be listed.Professor Sir Ian Gilmore, chair of the Alcohol Health Alliance UK, called the current rules “absurd”. “Shoppers who buy milk or orange juice have sugar content and nutritional information right at their fingertips,” he said. “But this information is not required when it comes to alcohol – a product not just fuelling obesity, but with widespread health harms and linked to seven types of cancer.” Miles Beale, who heads up the Wine and Spirit Trade Association, says members of the group want people to have access to nutritional information for all alcoholic drinks, but suggested the information should be carried online. “[We] have been pushing for greater information to be provided online,” said Mr Beale. “The alcohol industry can provide consumers with a far greater variety of information that is more relevant to consumers and which would not fit on a label,” he added. “There is significant variation in the number of calories in different alcoholic drinks and in different servings of drinks. Online is the best way to provide the volume and variety of information that consumers need to make quick and easy informed decisions. “It would also cost less to deliver.”‘WOMEN WERE BANNED’: The story of beauty queen Lea Campos’ fight to become a refereeIN TUNE: An eclectic mix featuring classical favourites, lesser-known gems and a few surprises

Parents face a trade-off between putting resources into their offspring versus using resources to enhance their chances of survival so they can have more offspring. The best allocation of resources depends on age. More experienced parents are better at getting food, so they can pass on more to their offspring. However, resources are needed to combat ‘wear and tear’, so in old age less can be passed on.
This increase-decrease pattern of allocation to offspring is seen in many mammals, birds and insects. Scientists at Bristol, with colleagues at Exeter and Oxford, found this pattern in an important disease-carrying insect, the tsetse fly. Tsetse flies give birth to live young that are nearly as big as their mother.
With colleagues at the Liverpool School of Tropical Medicine, the team studied tsetse mothers in the laboratory for their whole lives. Now, the team has made a mathematical model, published in the journal Proceedings of the Royal Society B, which to show how the pattern can be explained by changes the mothers experience as they get older.
Tsetse live on blood, which is a rich food supply but hard to get. The insects have to fly a long way to find an animal and avoid its defences, such as a swatting tail. Tsetse probably get better at acquiring food through experience, but the energy they need to fly increases as their wings become worn. Tsetse mothers have evolved to respond to these effects when passing on fat to their offspring.
“We expect that parents have evolved optimal patterns of resources allocation to maximise their reproductive success,” said lead author Dr. Antoine Barreaux, research associate at the University of Bristol and now lecturer in Intertryp at Cirad in France. “Our work takes into account age-dependence in many factors, such as feeding ability, energetic costs, and mortality.”
Dr. Sinead English from the School of Biological Sciences at the University of Bristol and leader of the team added: “Our model is the first to predict the initial increase and subsequent decrease with age of the allocation of resources by parents to their offspring.”
The mathematical model applies to all animals that have more than one offspring during their lives.
It predicts what strategic choices individuals will make depending on their ecology. Some species will allocate nearly everything to each breeding event, whereas others will build up their resources and reproduce less often. Explaining this diversity is an aim of the project.
“We hope that this theory inspires future tests with the data from long-term studies of wild populations such as red deer, bison or terns. This would allow scientists to come up with a general theory of investment by parents over their lives,” said Dr Barreaux
The team is developing the model to include the parasites that tsetse transmit. The hope is that a better understanding of these important insects will be used to reduce the transmission of diseases, such as sleeping sickness, to humans and livestock.
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As many as one in two patients stop taking statins, reduce the dose or take them irregularly because they believe the cholesterol-lowering drugs cause muscle pain and other side-effects. Now, a new study of over four million patients has shown that the true prevalence of statin intolerance worldwide is between six to ten percent.
The authors of the research, published in the European Heart Journal, say that their findings show that statin intolerance is over-estimated and over-diagnosed, with the result that patients are at greater risk of heart and blood vessel problems, including death, caused by high cholesterol levels.
There is strong and unambiguous evidence that statin treatment makes a significant difference in preventing cardiovascular disease and dying from it. Statins are among the most commonly prescribed drugs. However, until now, it has not been clear what proportion of people are truly intolerant of the drug, with inconsistent reports from studies, randomised controlled trials and databases suggesting it could range from 5-50%.
Researchers led by Professor Maciej Banach, of the Medical University of Lodz and the University of Zielona Góra, Poland, on behalf of the Lipid and Blood Pressure Meta-Analysis Collaboration and the International Lipid Expert Panel (ILEP), carried out a meta-analysis of 176 studies with 4,143,517 patients worldwide. The aim was to identify the overall prevalence of statin intolerance and the prevalence according to different diagnostic criteria. They also wanted to identify what factors might place people at greater risk of statin intolerance.
They found that the overall prevalence was 9.1%. Prevalence was even less when assessed according to diagnostic criteria from the National Lipid Association, the ILEP and the European Atherosclerosis Society: 7%, 6.7% and 5.9% respectively.
Prof. Banach said: “These results were not a surprise to me but they were for many other experts. They show that in most cases statin intolerance is over-estimated and over-diagnosed, and they mean that around 93% of patients on statin therapy can be treated effectively, with very good tolerability and without any safety issues.
“Our findings mean that we should evaluate patients’ symptoms very carefully, firstly to see whether symptoms are indeed caused by statins, and secondly, to evaluate whether it might be patients’ perceptions that statins are harmful — so called nocebo or drucebo effect — which could be responsible for more than 50% of all symptoms, rather than the drug itself.”
The researchers also found that people who were older, female, of Black or Asian race, obese, or suffering from diabetes, under-active thyroid glands, or chronic liver or kidney failure were more likely to be statin intolerant. In addition, drugs to control irregular heartbeat (arrhythmia), calcium channel blockers (often prescribed for chest pain and high blood pressure), alcohol use and higher statin doses were associated with a higher risk of statin intolerance. The increased risk of statin intolerance ranged from 22% (high alcohol consumption) to 48% (being female) in these groups.
“It is critically important to know about these risk factors so that we can predict effectively that a particular patient is at higher risk of statin intolerance. Then we can consider upfront other ways to treat them in order to reduce the risk and improve adherence to treatment. This could include lower statin doses, combination therapy and use of innovative new drugs,” said Prof. Banach.
The researchers acknowledge some limitations to their meta-analysis, such as differences between patients included in different studies, and lack of information on the amount of alcohol consumption and types of exercise. However, they have attempted to reduce the risk of bias from these, and this is helped by the large number of studies and patients included in the analysis.
“I believe the size of our study, which is the largest in the world to investigate this question, means we are able to finally and effectively answer the question about the true prevalence of statin intolerance,” said Prof. Banach. “These results clearly show that patients needn’t be afraid of statin therapy as it is very well tolerated in as much as 93%, which is similar or even better than other cardiology drugs, including ones for reducing blood pressure and clotting or blocking of blood vessels. What is more, patients need to know that statins may prolong their life, and in cases where side effects appear, we have enough knowledge to manage these effectively. The most important message to patients as a result of this study is that they should keep on taking statins according to the prescribed dose, and discuss any side effects with their doctor, rather than discontinuing the medication.
“The same clear message can be addressed to physicians treating patients with high cholesterol levels. Most cases of statin intolerance observed in clinical practice are associated with effects caused by patients’ misconceptions about the side effects of statins or may be due to other reasons. Therefore, we should carefully evaluate symptoms, assessing in detail patients’ medical histories, when the symptoms appeared, specific details of pain, other medications the patients are taking, and other conditions and risk factors. Then we will see that statins can be used safely in most patients, which is critically important for reducing their cholesterol levels and preventing heart and blood vessel diseases and death.”

In a scientific first, researchers at the University of California, Irvine have discovered fundamental mechanisms by which the hippocampus region of the brain organizes memories into sequences and how this can be used to plan future behavior. The finding may be a critical early step toward understanding memory failures in cognitive disorders such as Alzheimer’s disease and other forms of dementia.
Combining electrophysiological recording techniques in rodents with a statistical machine learning analysis of huge troves of data, the UCI researchers uncovered evidence suggesting that the hippocampal network encodes and preserves progressions of experiences to aid in decision-making. The team’s work is the subject of a paper published recently in Nature Communications.
“Our brain keeps a pretty good record of when specific experiences or events occur. This ability helps us function in our daily life, but before this study, we didn’t have a clear idea of the neuronal mechanisms behind these processes,” said corresponding author Norbert Fortin, UCI associate professor of neurobiology and behavior. “Where it connects with everybody is that this type of memory is strongly impaired in a variety of neurological disorders or simply with aging, so we really need to know how this brain function works.”
The project, which took more than three years to complete, involved experimental and data analysis phases. The researchers monitored the firing of neurons in rats’ brains as they underwent a series of odor identification tests. By presenting five different smells in various sequences, the scientists were able to measure the animals’ memory of the correct sequence and detect how their brains captured these sequential relationships.
“The analogy I would think about is computing,” Fortin said. “If I were to stick electrodes in your brain — we can’t; that’s why we use rats — I could see which cells are firing and which ones are not firing at any given moment. That provides us with some insight into how the brain represents and computes information. When we record activity patterns in a structure, it’s like we’re seeing zeros and ones in a computer.”
Obtained in millisecond intervals over several minutes, neuronal activity and inactivity measurements present a dynamic picture of the brain’s functioning. Fortin said that he and his colleagues were, in some ways, able to “read the minds” of their subjects by viewing the “coding” of the cells — which ones were firing and which were not — in rapid succession.

Two weeks makes a big difference in treating the animal version of HIV and latent tuberculosis, researchers from Texas Biomedical Research Institute, Southwest National Primate Research Center and colleagues report this month in the Journal of Clinical Investigation. The finding is another piece in the puzzle of the complex interaction between HIV and tuberculosis (TB), and can help advance development of therapies and a combined vaccine for the two diseases in humans.
“Most humans are able to control a low dose of TB infection by maintaining it in a dormant form called latent tuberculosis infection,” says Riti Sharan, PhD, a staff scientist at Texas Biomed and first paper author. “But if they get co-infected with HIV, then there is a high possibility that TB is reactivated and the patient ultimately dies of TB. Our objective is to improve existing interventions or identify new ones to prevent latent TB from being reactivated.”
To help study what happens in humans, researchers turn to nonhuman primates, which contract simian immunodeficiency virus (SIV), the monkey version of HIV, as well as tuberculosis. The researchers found that when animals with a latent TB infection start combined antiretroviral therapy (cART) against SIV two weeks after infection, the animals fare much better than if cART is started at four weeks post SIV infection.
“Originally, we did not think that two weeks would make this much of a difference, but to our surprise, it did,” Sharan says. “The findings were very dramatic and clear.”
Specifically, in the group that started cART at two weeks post infection, chronic immune activation was significantly reduced, as was SIV replication, and latent TB was not reactivated as much as in the group that started cART four weeks post infection. In fact, the lungs in the group that started treatment at four weeks looked more like they were not receiving any treatment at all.
Chronic, or ongoing, activation of an immune response, might sound like it should be a good thing to help fight illness. But it can also play a central role in exacerbating illness. When the immune cells are chronically activated, it leads to exhaustion and cell death, and this opens up a major gap in the body’s defense system, Sharan explains. That is when is appears latent tuberculosis can become reactivated.
“This paper adds to the growing body of evidence from our lab that shows chronic immune activation is key to driving reactivation of latent TB,” says Deepak Kaushal, PhD, a professor at Texas Biomed and senior paper author. “But it is the first to really look at the timing difference for administering ART in animal models, which is will be critical for future studies and helping develop treatments and vaccines.”
The researchers note that the difference of two weeks may not directly apply to humans, in part, because most people are unlikely to be diagnosed and begin treatment for HIV within two weeks of infection. The real value of the finding is identifying chronic immune activation as the main driver of latent TB reactivation following HIV infection, and now being able to study potential mechanisms for protection.
“Ultimately, we aim to use this information to design a therapy that would enable patients to prevent latent TB reactivation by limiting the HIV-driven chronic immune activation,” Sharan says.
The research was done in collaboration with the Emory University School of Medicine, Tulane National Primate Research Center and Washington University in St. Louis.
This investigation used resources supported by the Southwest National Primate Research Center grant P51 OD011133 from the National Institutes of Health Office of Research Infrastructure Programs.