Although antiretroviral therapy has made HIV a manageable disease, people living with HIV often suffer from chronic inflammation. This can put them at increased risk of comorbidities such as cardiovascular disease and neurocognitive impairment, affecting their longevity and quality of life. Now, a new study in Cell Reports explains why chronic inflammation occurs and how suppressing or even eliminating HIV in the body may not solve it.
In the study, researchers from George Washington University showed how an HIV protein permanently alters immune cells in a way that causes them to overreact to other pathogens. The study showed that when the protein is introduced into immune cells, genes in those cells associated with inflammation are activated, or expressed. These pro-inflammatory genes remain expressed, even when the HIV protein is no longer in the cells. According to the researchers, this “immune memory” of the original HIV infection is the reason that people living with HIV are prone to prolonged inflammation, which puts them at greater risk for cardiovascular disease and other comorbidities.
“This research highlights the importance of clinicians and patients realizing that suppressing or even eliminating HIV does not eliminate the risk of these serious comorbidities,” said Michael Pokrinski.And thesaid professor of microbiology, immunology, and tropical medicine in the GW School of Medicine and Health Sciences and lead author of the study. “Patients and their physicians should discuss ways to reduce inflammation and researchers should continue to pursue potential therapeutic targets that can reduce inflammation and comorbidities in patients with HIV.”
For the study, the research team isolated human immune cells in the laboratory and exposing them to HIV Nef. The amount of Nef that is introduced into the cells is similar to the amount found in about half of the HIV-infected people taking antiretrovirals whose HIV pregnancy cannot be detected. After a period of time, the researchers introduced a bacterial toxin to generate an immune response from cells exposed to Nef. Compared to cells that were not exposed to the HIV protein, cells exposed to Nef produced an elevated level of inflammatory proteins, called cytokines. When the team compared the genes of cells exposed to Nef with those of cells not exposed to Nef, they identified pro-inflammatory genes that were in a state ready to be expressed as a result of exposure to Nef.
According to Pokrinsky, the findings in this study could help explain why some comorbidities persist after other viral infections, including COVID-19.
“We have seen this pro-inflammatory immune memory being reported with other pathogens and it is often referred to as ‘trained immunity,’” Pokrinsky explains. “While this ‘trained immunity’ has evolved as a useful immune process to protect against new infection, it may In some cases, it leads to satisfactory results. The final effect depends on the length of this memory, and extended memory may underlie long-lived inflammatory states as we see in prolonged HIV or COVID infections.”
The paper, “Extracellular vesicles harbor HIV-1 Nef prolonged hyperactivity of myeloid cells,” will be published in Cell Reports On November 14, the National Heart, Lung, and Blood Institute of the National Institutes of Health supported this research.