People living with HIV have a greater risk of developing lung diseases like COPD and emphysema at a younger age, even if they have never smoked. That’s according to a paper, “HIV Disrupts the Lung Molecular Clock, Leading to Lung Inflammation and Features of Emphysema,” published in Communications Biology.
Researchers at Florida International University (FIU) in Miami have uncovered a previously unknown mechanism in the form of an HIV protein known as Tat (trans-activator of transcription). According to a press release, this protein can disrupt the lungs’ internal molecular “clock,” which regulates daily lung function and plays a key role in immune response. This disruption can cause chronic inflammation that damages airway tissue and sets the stage for disease.
“This is the first study to show HIV is interfering with this important system,” said Hoshang Unwalla, PhD, lead study author and professor at the FIU Herbert Wertheim College of Medicine. “It opens the door for new ways to potentially slow or prevent disease development.”
In the study, the researchers led a series of experiments using lung samples from HIV patients along with lab-grown lung cells and a mouse model engineered to produce Tat exclusively in the lungs. They found Tat increased levels of a small regulatory molecule, which had a domino effect. The molecule shut down production of the SIRT1 protein, which keeps the internal clock running in the lungs, resulting in more inflammatory molecules being present.
In the mouse model, early signs of emphysema began to appear at around four months of age, the equivalent to about age 25 in humans. The research also looked at ways to potentially reset the clock.
“When we treated the cells with the SIRT1 activator, we were able to reduce the inflammatory molecules,” said Kingshuk Panda, PhD candidate in Dr. Unwalla’s lab. “This suggests that if we can target this pathway, we may be able to improve outcomes.”
The findings could have implications beyond the lungs, authors noted, because trillions of genes are present throughout the body. Dr. Unwalla said Tat could be dysregulating clocks in other organs as well.
