Cure for HIV moves closer as scientists find potential genetic switch

Agencies
December 7, 2018

Washington, Dec 7: A genetic switch that causes HIV hidden inside the cells to replicate can be manipulated to completely eradicate the virus from the human body, a study has found.

Cells harbouring latent HIV are "invisible" to the natural defences of the immune system, said researchers from the University of Illinois at Chicago in the US.

During infection, the DNA of HIV makes its way into the host cell's nucleus and integrates itself into the host genome.

The Tat gene circuit is a key piece of HIV DNA that controls the HIV gene transcription and activation, according to the study published in the journal Proceedings of the National Academy of Sciences.

When activated, it initiates a takeover of the cell's machinery to churn out new copies of the HIV virus, which eventually burst from the cell and infect neighbouring cells.

HIV-specific immune effector cells kill cells infected with HIV, but only when the cells are being used to produce more of the virus, meaning that the Tat gene circuit is switched on.

In cells that are latently infected, the Tat gene circuit is off, and the cell goes about its normal business all the while harbouring quiescent HIV.

"By targeting the Tat gene circuit with drugs or small molecules to activate it, we would be able to cause latently-infected cells to start producing more virus, and then they can be destroyed by the immune system," said Jie Liang, a professor at the University of Illinois.

So far, there are no drugs successfully targeting this circuit, researchers said.

People infected with the HIV virus can live relatively normal lives with exceedingly low or even undetectable viral loads thanks to powerful antiretroviral therapies that work to suppress viral replication.

However, even in people where the virus is undetectable, it doesn't mean it's completely absent.

The HIV virus can hide in cells in an inactivated state, meaning it isn't actively replicating.

This is a dire situation and makes life-long antiretroviral therapy the only option for HIV infected patients.

"It is extremely difficult to flush latently-infected cells out of their latency," Liang said.

Techniques developed to reactivate latent HIV-infected cells so that they become susceptible to the body's natural immune response or to drug therapies have had mixed results.

This is mostly because the technique, known as "shock and kill," relies on a class of drugs called HDAC inhibitors that come with severe adverse effects, researchers said.

"We need to better understand the mechanisms that regulate HIV latency so we can identify new opportunities for intervention and develop better drugs that can either lock viral particles in a latent state, or kill latent cells, or both," Liang said.

The Tat gene circuit has a random probability of being active or inactive, and the switch from inactive to active can happen spontaneously.

"In HIV-infected cells, reactivation of the Tat gene circuit is still a very rare event," Liang said.

The researchers developed advanced computational algorithms to study the Tat gene circuit under different conditions.

"Using different models and algorithms, we were able to accurately map a 'probability landscape' of the cellular reactions that can impact Tat gene circuit reactivation, and our results suggest new ways of targeting latent cells that may lead to the eradication of the HIV virus from a host," Liang said.

Researchers identified ways to manipulate the Tat gene circuit so that the "shock and kill" technique would be more effective.

They also looked at a "block and lock" strategy, where latent viral particles are locked into latency by permanently blocking activation of the Tat gene circuit.

"Our results suggest that by controlling HIV latency through manipulation of the Tat gene circuit, effective therapeutic strategies can be identified that would one day provide a cure for HIV," Liang said.

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News Network
February 21,2020

Washington, Feb 21: The fat around arteries may play an important role in keeping the blood vessels healthy, according to a study in rats that may affect how researchers test for treatments related to plaque buildup, as seen in conditions leading to heart attack.

The study, published in the journal Scientific Reports, noted that the fat, known as perivascular adipose tissue, or PVAT, helps arteries let go of muscular tension while under constant strain.

According to the researchers, including Stephanie W. Watts from the Michigan State University in the US, this feature is similar to how the bladder expands to accommodate more liquid, while at the same time keeping it from spilling out.

"In our study, PVAT reduced the tension that blood vessels experience when stretched," Watts said.

"And that's a good thing, because the vessel then expends less energy. It's not under as much stress," she added.

According to Watts and her team, PVAT has largely been ignored by researchers believing its main job was to store lipids and do little more.

Until now, she said, scientists only divided blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media, and the outermost layer called the tunica adventitia.

Watts believes PVAT is the fourth layer, which others have called tunica adiposa.

Tunica, she said, meant a membranous sheath enveloping or lining an organ, and adiposa is a synonym for fat.

"For years, we ignored this layer -- in the lab it was thrown out. In the clinic it wasn't imaged. But now we're discovering it may be integral to our blood vessels," Watts said.

"Our finding redefines what the functional blood vessels are, and is part of what can be dysfunctional in diseases that afflict us, including hypertension. We need to pay attention to this layer of a blood vessel because it does far more than we originally thought," she added.

Earlier studies, Watts said, had shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

In the current study, the researchers decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

They tested the thoracic aorta in rats, and found those with intact PVAT had more stress relaxation than those without.

The study revealed that the pieces of artery with surrounding fat had measurably relaxed more than those without.

Watts and her colleagues then tested other arteries, and were able to duplicate the same response.

"It's not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it's a general phenomenon," she said.

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Agencies
April 15,2020

Dear parents, if you want your children to have proper sleep, read this carefully. Joining a growing list of studies that tell parents to shun devices at bed-time, researchers say that children who use devices and decide what time they go to sleep, achieve less sleep and feel more sleepier the following day than their peers.

The study of children in this age-group (aged 11 to 13 years), published in the New Zealand Medical Journal, found most (72 per cent) of the 163 students interviewed by University of Otago researchers achieved recommended guidelines of an average 9 to 11 hours sleep nightly over one week.

"But that also means that almost one in four students did not achieve sleep within these guidelines, which highlights an area for improvement," said study researcher Kate Ford.

However, consistent with previous research in 15 to 17-year-old New Zealanders, the study results show less sleep on the nights where devices are used in the hour before bed.

According to the researchers, students who used devices before going to sleep were also more likely to report that they felt sleepy the following morning. Watching television before bed had no significant effect on sleep length.

There were also some interesting observations over the weekends where students went to bed later but woke later achieving similar sleep length to the school days, the researchers said.

A small group of students (six per cent) who reported less than seven hours of sleep, including a small number reporting not sleeping at all, according to the study,

Therefore, while the average across the week of 72 per cent of students reporting adequate sleep is reassuring, it is far from the goal of every child achieving sleep within the recommended guidelines," Ford said.

Dr Paul Kelly, head of the Sleep Health Service at Canterbury District Health Board, supervised the study and explained that the foundations for good health are based on proper nutrition, regular exercise and good sleep quality.

Sleep quality is often overlooked as a contributory factor to poor health.

"The study findings suggest the need for parental guidance around bedtimings and moderation of the use and availability of electronic devices before bed," Kelly said.

"Respect and protect your sleep, as good daytime functioning is reliant on adequate sleep," Kelly added.

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News Network
June 20,2020

Washington, Jun 20: Pregnant and postpartum women are usually at a high risk of depression and anxiety - one in seven women struggle with symptoms in the perinatal period and the coronavirus pandemic is exacerbating those struggles according to a recent study.

The study was published in Frontiers in Global Women's Health, which found that the likelihood of maternal depression and anxiety has substantially increased during the health crisis.

"The social and physical isolation measures that are critically needed to reduce the spread of the virus are taking a toll on the physical and mental health of many of us," said Dr. Margie Davenport of the University of Alberta, Canada, who co-authored the study.

For new moms, those stresses come with side effects.

"We know that experiencing depression and anxiety during pregnancy and the postpartum period can have detrimental effects on the mental and physical health of both mother and baby that can persist for years," said Davenport.

Such effects can include premature delivery, reduced mother-infant bonding, and developmental delays in infants.

The study surveyed 900 women - 520 of whom were pregnant and 380 of whom had given birth in the past year - and asked about their depression and anxiety symptoms before and during the pandemic.

Before the pandemic began, 29 percent of those women experienced moderate to high anxiety symptoms, and 15 percent experienced depressive symptoms. During the pandemic, those numbers increased - 72 percent experienced anxiety and 41percent experienced depression.

Because lockdown measures have affected daily routines and access to gyms, researchers also asked women whether their exercise habits had changed. Of the women surveyed, 64 percent reduced their physical activity since the pandemic began, while 15 percent increased and 21 percent experienced no change.

Exercise is a known way to ease depression symptoms, so limited physical activity may result in an uptick in depressive symptoms. Indeed, the study found that women who engaged in at least 150 minutes of moderate physical activity a week had significantly lower symptoms of depression and anxiety.

The findings are somewhat limited given the fact that researchers could not survey women before the pandemic began (since they could not know a pandemic would occur). The women surveyed could only offer their pre-pandemic symptoms in hindsight.

Also, while the researchers asked women about their symptoms using validated measures, only mental health care professionals can validly diagnose an individual with depression or anxiety.

The study was specifically interested in the impact of COVID-19 on new moms, but Davenport says maternal mental health is a critical issue no matter the time.

"Even when we are not in a global pandemic, many pregnant and postpartum women frequently feel isolated whether due to being hospitalized, not having family or friends around or other reasons," she said.

"It is critical to increase awareness of the impact of social (and physical) isolation on the mental health of pregnant and postpartum women," Davenport added.

Increased awareness makes diagnosis and treatment - the ultimate goal - more likely.

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