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
July 10,2020

Toronto, Jul 10: Pasteurising breast milk at 62.5 degrees Celsius for 30 minutes inactivates the SARS-CoV-2 virus that causes Covid-19, making it safe for consumption by babies, a study claims.

According to the research published in the Canadian Medical Association Journal, current advice for women with Covid-19 is to continue to breastfeed their own infants.

In Canada, it is standard care to provide pasteurised breast milk to very-low-birth-weight babies in hospital until their own mother's milk supply is adequate, the researchers said.

"In the event that a woman who is Covid-19-positive donates human milk that contains SARS-CoV-2, whether by transmission through the mammary gland or by contamination through respiratory droplets, skin, breast pumps and milk containers, this method of pasteurisation renders milk safe for consumption," said Sharon Unger, a professor at the University of Toronto in Canada.

The Holder method, a technique used to pasteurise milk in all Canadian milk banks at 62.5 degrees Celsius for 30 minutes, is effective at neutralising viruses such as HIV, hepatitis and others that are known to be transmitted through human milk, the researchers said.

In the latest study, the researchers spiked human breast milk with a viral load of SARS-CoV-2 and tested samples that either sat at room temperature for 30 minutes or were warmed to 62.5 degrees Celsius for 30 minutes.

They then measured for active virus, finding that the virus in the pasteurised milk was inactivated after heating.

More than 650 human breast milk banks around the world use the Holder method to ensure a safe supply of milk for vulnerable infants, the researchers said.

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News Network
February 26,2020

New York, Feb 26:  A new wearable sensor that works in conjunction with artificial intelligence (AI) technology could help doctors remotely detect critical changes in heart failure patients days before a health crisis occurs, says a study.

The researchers said the system could eventually help avert up to one in three heart failure readmissions in the weeks following initial discharge from the hospital and help patients sustain a better quality of life.

"This study shows that we can accurately predict the likelihood of hospitalisation for heart failure deterioration well before doctors and patients know that something is wrong," says the study's lead author Josef Stehlik from University of Utah in the US.

"Being able to readily detect changes in the heart sufficiently early will allow physicians to initiate prompt interventions that could prevent rehospitalisation and stave off worsening heart failure," Stehlik added.

According to the researchers, even if patients survive, they have poor functional capacity, poor exercise tolerance and low quality of life after hospitalisations.

"This patch, this new diagnostic tool, could potentially help us prevent hospitalizations and decline in patient status," Stehlik said.

For the findings, published in the journal Circulation: Heart Failure, the researchers followed 100 heart failure patients, average age 68, who were diagnosed and treated at four veterans administration (VA) hospitals in Utah, Texas, California, and Florida.

After discharge, participants wore an adhesive sensor patch on their chests 24 hours a day for up to three months.

The sensor monitored continuous electrocardiogram (ECG) and motion of each subject.

This information was transmitted from the sensor via Bluetooth to a smartphone and then passed on to an analytics platform, developed by PhysIQ, on a secure server, which derived heart rate, heart rhythm, respiratory rate, walking, sleep, body posture and other normal activities.

Using artificial intelligence, the analytics established a normal baseline for each patient. When the data deviated from normal, the platform generated an indication that the patient's heart failure was getting worse.

Overall, the system accurately predicted the impending need for hospitalization more than 80 per cent of the time.

On average, this prediction occurred 10.4 days before a readmission took place (median 6.5 days), the study said.

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Agencies
May 8,2020

As Europe and the US loosen their lockdowns against the coronavirus, health experts are expressing growing dread over what they say is an all-but-certain second wave of deaths and infections that could force governments to clamp back down.

"We are risking a backslide that will be intolerable," said Dr Ian Lipkin of Columbia University's Center for Infection and Immunity.

Around the world, German authorities began drawing up plans in case of a resurgence of the virus. Experts in Italy urged intensified efforts to identify new victims and trace their contacts. And France, which has not yet eased its lockdown, has already worked up a "reconfinement plan" in the event of a new wave.

"There will be a second wave, but the problem is to which extent. Is it a small wave or a big wave? It is too early to say," said Olivier Schwartz, head of the virus unit at France's Pasteur Institute.

In the US, with about half of the states easing their shutdowns to get their economies restarted and cellphone data showing that people are becoming restless and increasingly leaving home, public health authorities are worried.

Many states have not put in place the robust testing that experts believe is necessary to detect and contain new outbreaks. And many governors have pressed ahead before their states met one of the key benchmarks in the Trump administration's guidelines for reopening -- a 14-day downward trajectory in new illnesses and infections.

"If we relax these measures without having the proper public health safeguards in place, we can expect many more cases and, unfortunately, more deaths," said Josh Michaud, associate director of global health policy with the Kaiser Family Foundation in Washington.

Cases have continued to rise steadily in places such as Iowa and Missouri since the governors began reopening, while new infections have yo-yoed in Georgia, Tennessee and Texas.

Lipkin said he is most worried about two things: the reopening of bars, where people crowd together and lose their inhibitions, and large gatherings such as sporting events, concerts and plays. Preventing outbreaks will require aggressive contact tracing powered by armies of public health workers hundreds of thousands of people strong, which the US does not yet have, Lipkin said.

Worldwide the virus has infected more than 36 lakh people and killed over a quarter-million, according to a tally by Johns Hopkins University that experts agree understates the dimensions of the disaster because of limited testing, differences in counting the dead and concealment by some governments.

The US has recorded over 70,000 deaths and 12 lakh confirmed infections, while Europe has reported over 140,000 dead.

This week, the researchers behind a widely cited model from the University of Washington nearly doubled their projection of deaths in the US to around 134,000 through early August, in large part because of the easing of state stay-at-home restrictions. Newly confirmed infections per day in the US exceed 20,000 and deaths per day are running well over 1,000.

In hard-hit New York City, which has managed to bring down deaths dramatically even as confirmed infections continue to rise around the rest of the country, Mayor Bill de Blasio warned that some states may be reopening too quickly.

"My message to the rest of the country is learn from how much effort, how much discipline it took to finally bring these numbers down and follow the same path until you are sure that it is being beaten back," he said on CNN, "or else, if this thing boomerangs, you are putting off any kind of restart or recovery a hell of a lot longer."

A century ago, the Spanish flu epidemic's second wave was far deadlier than its first, in part because authorities allowed mass gatherings from Philadelphia to San Francisco.

"It is clear to me that we are in a critical moment of this fight. We risk complacency and accepting the preventable deaths of 2,000 Americans each day," epidemiologist Caitlin Rivers, a professor at Johns Hopkins, told a House subcommittee in Washington.

President Donald Trump, who has pressed hard to ease the restrictions that have throttled the economy and thrown more than three crore Americans out of work, pulled back Wednesday on White House plans revealed a day earlier to wind down the coronavirus task force.

He tweeted that the task force will continue meeting indefinitely with a "focus on SAFETY & OPENING UP OUR COUNTRY AGAIN".

Underscoring those economic concerns, the European Union predicted the worst recession in its quarter-century history. And the US unemployment rate for April, which comes out on Friday, is expected to hit a staggering 16 per cent, a level last seen during the Great Depression of the 1930s.

Governors continue to face demands, even lawsuits, to reopen. In Michigan, where armed demonstrators entered the Capitol last week, the Republican-led Legislature sued Democratic Governor Gretchen Whitmer, asking a judge to declare invalid her stay-at-home order, which runs at least through May 15.

In hard-hit Italy, which has begun easing restrictions, Dr Silvio Brusaferro, president of the Superior Institute of Health, urged "a huge investment" of resources to train medical personnel to monitor possible new cases of the virus, which has killed about 30,000 people nationwide.

He said that contact-tracing apps which are being built by dozens of countries and companies are not enough to manage future waves of infection.

German Chancellor Angela Merkel said after meeting with the country's 16 governors that restaurants and other businesses will be allowed to reopen in the coming weeks but that regional authorities will have to draw up a "restriction concept" for any county that reports 50 new cases for every 100,000 inhabitants within a week.

Lothar Wieler, head of Germany's national disease control centre, said scientists "know with great certainty that there will be a second wave" of infections.

Britain, with over 30,000 dead, the second-highest death toll in the world behind the US, plans to extend its lockdown but has begun recruiting 18,000 people to trace contacts of those infected.

In other developments, the US Centers for Disease Control and Prevention said nearly 5,000 coronavirus illnesses and at least 88 deaths have been reported among inmates in American jails and prisons. An additional 2,800 cases and 15 deaths were reported among guards and other staff members.

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