0

0

0

0

0

0

0

0

0

In This Article

Immune system’s most wanted: how the HIV protein got caught
89

Immune system’s most wanted: how the HIV protein got caught

HIV can’t hide for long. Researchers have found a way to not only tail the elusive virus but also target it in treatment.

Immune system’s most wanted: how the HIV protein got caughtLike a criminal evading arrest, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) has managed to stay maddening steps ahead of our immune teams hunting it down. The virus relies on a shifty protein sidekick called Nef, which wipes clean “wanted” markers on infected cells’ surfaces, helping HIV hide in plain sight.

But the University of Pittsburgh researchers have engineered targeted seek-and-destroy agents — PROTACs — that can infiltrate cells undercover, slip past Nef’s counterintelligence, and radio in precise coordinates of infection. PROTACs biochemically tag rogue Nef proteins, which signals cellular protein shredders and scavengers to take out the trash.

As a promising new avenue for the treatment of HIV and AIDs, here is how the novel therapy works.

A mysterious protein and a blood bank cohort

For decades, the Nef protein has intrigued HIV scientists. The case of the ‘Sydney Blood Bank Cohort”, however, proved revealing. For 29 years, researchers have monitored a group of blood recipients who were accidentally infected by an HIV-positive donor. The catch was the donor had an HIV strain missing its sneaky Nef protein.

All eight had either low or absent viral replication for up to 29 years. In one case, ‘Subject C135’ even managed to clear his infection, without any medication.

Recent findings from this natural experiment showcase how even weakened HIV can vary wildly in virulence across hosts. But absent Nef appears consistently vital for viral cover and takeover given non-progression across the cohort. This is why targeting Nef could be a game-changer for HIV-medicine.

Professor Attili Venkata Satya Suresh, a Medical Oncologist and haematologist at Continental Hospitals in Hyderabad, suggests that Nef has been demonstrated in both animal and human studies to be crucial for the propagation of the HIV virus, resulting in the depletion of CD4 immune cells and contributing to the severity of AIDS or immunodeficiencies.

When specific products targeting Nef are not adequately used, dysfunction is anticipated. “If this essential component becomes inactive, the virus may induce less severe AIDS or HIV-related immunosuppression,” adds Professor Suresh.

The PROTAC strategy

As Nef lacks an active site and enzymatic function, conventional drugs that rely on directly binding to active sites face difficulties in development, leading researchers to explore alternative approaches.

Researchers from the University of Pittsburgh School of Medicine, US, wanted a way to better mark Nef, so the immune system could do its job. They developed a tool — proteolysis-targeting chimeras — which are like ‘tags’ that stick to unwanted proteins in our cells, signalling the cell’s garbage disposal to break down and remove those proteins.

The researchers started by looking for places to attach linkers on the compounds that do bind to Nef. They then connected these compounds to molecules that recruit cellular machinery for protein degradation. After work on 102 unique PROTACS, they found that they were able to trigger Nef protein breakdown.

When tested in cells, these PROTACs successfully reversed the effects caused by Nef, like restoring certain immune system markers on the cell surface and reducing the replication of the HIV-1 virus.

Professor Suresh adds, “PROTAC strategy can be considered very safe from a technical standpoint. It can complement conventional medications without requiring significant adjustments to the treatment regimen.”

The preprint paper’s lead author, Thomas E Smith, said the study presents the potential of PROTACs in degrading microbial proteins, broadening the spectrum of therapeutic options.

Also read: Researchers use a cell’s recycling process to combat blood cancers

Related Tags

Related Posts

Share Your Experience/Comments

Leave a Reply

Your email address will not be published. Required fields are marked *

Summit Registration

NOTE: The summit will be held at NIMHANS Convention Centre, Bengaluru.

Wellness Registration Form

-
-
-
Total Amount INR 3000
Trending

Articles

Article
Some couples consciously decide not to have children despite familial and social expectations, wanting to make the best of their relationship. Children should be had for their own sake, says psychotherapist Tasneem Nakhoda
Article
Insufficient consumption of heart-healthy foods can affect cardiovascular health. Experts discuss beneficial dietary choices
Article
Cycling and walking are both great cardiovascular activities that aid weight loss and keep various health conditions away. Pick one that suits your fitness goals and physical condition, say experts
Article
Summer drinks, though hydrating, can have excess sugar. Nutritionists suggest a few alternatives to keep the body temperature and sugar levels down
Article
Packed with protein, this recipe will help in weight management by keeping you full for a long time
Article
Researchers have found that a quick snooze can improve the retention of information by strengthening memories, leading to better recollection over an extended period
Trending

Articles

Article
Some couples consciously decide not to have children despite familial and social expectations, wanting to make the best of their relationship. Children should be had for their own sake, says psychotherapist Tasneem Nakhoda
Article
Insufficient consumption of heart-healthy foods can affect cardiovascular health. Experts discuss beneficial dietary choices
Article
Cycling and walking are both great cardiovascular activities that aid weight loss and keep various health conditions away. Pick one that suits your fitness goals and physical condition, say experts

0

0

0

Web Stories 

0

0

0

0

0

0

Opt-in To Our Daily Newsletter

* Please check your Spam folder for the Opt-in confirmation mail

Opt-in To Our
Daily Newsletter

We use cookies to customize your user experience, view our policy here

Your feedback has been submitted successfully.

The Happiest Health team will reach out to you at the earliest