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.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.
News Network
May 11,2020

Panaji, May 11: Amid the COVID-19 outbreak, most of the people are more concerned about the health of their near and dear ones than their own well-being, says a study conducted by a leading business school in Goa.

People are now more conscious about any bodily changes, and even mild cold, cough and sneezing, it says.

The study, on public's reaction towards COVID-19 outbreak by gauging their psychological response in terms of anxiety and their coping behaviour, was conducted by the Goa Institute of Management's Dr Divya Singhal and Prof Padhmanabhan Vijayaraghavan.

It took into account inputs from 231 respondents residing in various parts of the country.

"Nearly 82.25 per cent of the respondents were more worried about the health of their loved ones than their own well-being," Singhal said.

"Majority of the respondents have become conscious of any bodily changes, sensations, a mild cold, cough, sneezing and experience concern, and attribute those changes to the symptoms of COVID-19," she said.

Besides, more than 50 per cent of the respondents said their social media usage has gone up as well as their time spent on watching movies and shows through online medium, the official said.

The respondents agreed that their technology usage to connect with friends and relatives has gone up, she said.

The study also indicated that a large group of respondents found it "depressing" to read forwarded messages on the deadly disease.

"An overwhelming majority of the respondentsagreed that they discourage unverified forwarded messages about COVID-19 on social media," says the study.

It also found that 41 per centof the respondents were not doing any physical activity, like yoga, during the lockown period, while another 19 per cent were not sure about engaging themselves in physical activities.

Besides, 57 per cent of the respondents were not engaged in any mind-calming practices like meditation, and 18 per cent were not sure about taking up meditative practices, the study said.

The respondents included 145 men and 86 women, aged 18 and above, with nearly 60 per cent of them residing in non- metro cities and rest from metros.

About 47.62 per cent of the respondents were employed in private or government sectors, and the remaining included students, retired persons and homemakers.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.
Agencies
May 10,2020

Washington D.C., May 9: Do the middle age feel much stressful now, and seems to have changed over time, if compared to the life in the 90s? Well, this recent study indicates that it might be true.

The study has signalled to the fact that life may become more stressful majorly for middle-aged people than it was in the 1990s. The researchers reached this analysis even before the novel coronavirus started sweeping the globe.

A team of researchers led by Penn State found that across all ages, there was a slight increase in daily stress in the 2010s compared to the 1990s. But when researchers restricted the sample to people between the ages of 45 and 64, there was a sharp increase in daily stress.

"On average, people reported about 2 percent more stressors in the 2010s compared to people in the past," said David M. Almeida, professor of human development and family studies at Penn State.

"That's around an additional week of stress a year. But what really surprised us is that people at mid-life reported a lot more stressors, about 19 percent more stress in 2010 than in 1990. And that translates to 64 more days of stress a year."

Almeida said the findings were part of a larger project aiming to discover whether health during the middle of Americans' lives has been changing over time.

"Certainly, when you talk to people, they seem to think that daily life is more hectic and less certain these days," Almeida said.

For the study, the researchers collected data from 1,499 adults in 1995 and 782 different adults in 2012.

Almeida said the goal was to study two cohorts of people who were the same age at the time the data was collected but born in different decades. All study participants were interviewed daily for eight consecutive days.

During each daily interview, the researchers asked the participants about their stressful experiences throughout the previous 24 hours.

They asked questions related to arguments with family or friends or feeling overwhelmed at home or work, so and so. The participants were also asked how severe their stress was and whether those stressors were likely to impact other areas of their lives.

"We were able to estimate not only how frequently people experienced stress, but also what those stressors mean to them," Almeida said.

"For example, did this stress affect their finances or their plans for the future. And by having these two cohorts of people, we were able to compare daily stress processes in 1990 with daily stress processes in 2010," Almeida added.

After analyzing the data, the researchers found that participants reported significantly more daily stress and lower well-being in the 2010s compared to the 1990s.

Additionally, participants reported a 27 percent increase in the belief that stress would affect their finances and a 17 percent increase in the belief that stress would affect their future plans.

Almeida said he was surprised not that people were more stressed now than in the 90s, but at the age group that was mainly affected.

"We thought that with economic uncertainty, life might be more stressful for younger adults. But we didn't see that. We saw more stress for people at mid-life," Almeida said.

"And maybe that's because they have children who are facing an uncertain job market while also responsible for their own parents. So it's this generational squeeze that's making stress more prevalent for people at mid-life," he concluded.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.
Agencies
March 15,2020

Should you let your babies "cry it out" or rush to their side? Researchers have found that leaving an infant to 'cry it out' from birth up to 18 months does not adversely affect their behaviour development or attachment.

The study, published in the Journal of Child Psychology and Psychiatry, found that an infant's development and attachment to their parents is not affected by being left to "cry it out" and can actually decrease the amount of crying and duration.

"Only two previous studies nearly 50 or 20 years ago had investigated whether letting babies 'cry it out' affects babies' development. Our study documents contemporary parenting in the UK and the different approaches to crying used," said the study's researcher Ayten Bilgin from the University of Warwick in the UK.

For the study, the researchers followed 178 infants and their mums over 18 months and repeatedly assessed whether parents intervened immediately when a baby cried or let the baby let it cry out a few times or often.

They found that it made little difference to the baby’s development by 18 months.

The use of parent’s leaving their baby to ‘cry it out’ was assessed via maternal report at term, 3, 6 and 18 months and cry duration at term, 3 and 18 months.

Duration and frequency of fussing and crying was assessed at the same ages with the Crying Pattern Questionnaire.

According to the researchers, how sensitive the mother is in interaction with their baby was video-recorded and rated at 3 and 18 months of age.

Attachment was assessed at 18 months using a gold standard experimental procedure, the strange situation test, which assesses how securely an infant is attached to the major caregiver during separation and reunion episodes.

Behavioural development was assessed by direct observation in play with the mother and during assessment by a psychologist and a parent-report questionnaire at 18 months.

Researchers found that whether contemporary parents respond immediately or leave their infant to cry it out a few times to often makes no difference on the short - or longer term relationship with the mother or the infants behaviour.

This study shows that 2/3 of mum's parent intuitively and learn from their infant, meaning they intervene when they were just born immediately, but as they get older the mother waits a bit to see whether the baby can calm themselves, so babies learn self-regulation.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.