Florida International University Study Finds HIV Disrupts Lung “Clock,” Increasing COPD and Emphysema Risk

Florida International University researchers have identified a specific mechanism by which HIV increases the risk of chronic obstructive pulmonary disease and emphysema, even in individuals who have never smoked. The study, published in Communications Biology, reveals that the HIV protein Tat disrupts the lungs’ internal molecular clock, leading to chronic inflammation and lung tissue damage.

According to lead study author Hoshang Unwalla, professor at the FIU Herbert Wertheim College of Medicine, Tat interferes with the timekeeping system that regulates daily lung function and immune response. This disruption triggers a cascade of inflammatory molecules that damage airway tissue and set the stage for disease development.

The research team found that Tat increases levels of a small regulatory molecule, which in turn suppresses the production of SIRT1, a protein essential for maintaining the lung’s molecular clock. With SIRT1 inhibited, core circadian genes such as BMAL1 and PER2 become dysregulated, impairing the lung’s ability to manage inflammation and repair.

Unwalla’s lab has spent decades studying HIV’s effects on the lungs and was among the first to demonstrate that the virus can infect airway cells and form persistent reservoirs. These reservoirs continue to produce harmful proteins like Tat, even in individuals undergoing antiretroviral therapy, contributing to ongoing lung damage.

To investigate the mechanism, researchers conducted experiments using lung samples from HIV patients, lab-grown lung cells, and a mouse model engineered to express Tat exclusively in the lungs. In these models, they observed significant alterations in clock gene expression and elevated markers of inflammation, confirming the role of the Tat/miR-126-3p/SIRT1 axis in driving lung pathology.

The findings suggest that targeting this molecular pathway could offer new strategies to slow or prevent the development of HIV-associated COPD and emphysema. By restoring normal circadian function in the lungs, it may be possible to reduce chronic inflammation and protect lung tissue in people living with HIV.

As the HIV-positive population ages, comorbid lung diseases have become a major contributor to morbidity and mortality. This study provides a clearer understanding of how HIV directly impacts lung health beyond traditional risk factors like smoking, highlighting circadian dysregulation as a key driver of disease in this population.