HIV may cause emphysema when it bonds to and manipulates airway stem cells, according to researchers.
The virus reprograms the stem cells, called basal cells, to produce enzymes that can destroy lung tissue, they wrote in Cell Reports.
“This research is important because although antiretroviral agents have turned HIV into a chronic, rather than deadly, disease, the viral reservoirs that remain in the lungs and other tissue continue to cause serious side effects,” study author Ronald G. Crystal, MD, chairman of the department of genetic medicine at Weill Cornell Medicine and a pulmonologist at New York Presbyterian/Weill Cornell Medical Center, said in a news release. “Now that we have more information about how the HIV virus might cause emphysema, we can learn more about this potential enzyme target and work toward developing a therapy to prevent this lung damage from happening.”
The researchers collected basal cells from the lungs of healthy nonsmokers, exposed them to increasing levels of HIV for 2 days and compared the results with those in a control group of cells not infected with the virus.
They found that mRNA expression for the enzyme matrix metalloprotease-9 (MMP-9) — which can break down proteins and destroy tissue — increased according to the dosage of HIV in the infected cells (P < .05).
MMP-9 secretion increased by 18.7 ng/mL in HIV–exposed cells, compared with 8 ng/mL in the control group (P < .002), and by 12.6 ng/mL in those exposed to both HIV and 3% cigarette smoke extract (CSE), compared with 5.9 ng/mL in the control cells (P < .0001).
Likewise, MMP-9 secretion increased by 10 ng/mL in cells exposed to HIV and 6% CSE, compared with 4.1 ng/mL in control cells (P < .001). MMP-9 levels in cells exposed to heat-inactivated HIV were comparable to those in control cells, the researchers said.
Citing previous data that showed MMP-9 was present in lung areas affected by emphysema, they said that HIV could be a cause for the disease via production of the protease.
“Our next step is to conduct additional research to determine what the preventive therapeutic target might be,” Crystal said. “and then, since basal cells are so important to normal lung anatomy and lung function, determine the other side effects of this reprogramming.” – by Joe Green
Disclosure: The authors report no relevant financial disclosures.