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 developing comorbidities such as cardiovascular disease and neurocognitive dysfunction, which impacts their longevity and quality of life. Now, a new study in Cell Reports explains why chronic inflammation can occur and how suppressing or even eradicating HIV from the body may not solve it.
In the study, researchers from George Washington University show how an HIV protein permanently alters immune cells in a way that causes them to overreact to other pathogens. When the protein is introduced into immune cells, genes in those cells associated with inflammation become activated or expressed, the study showed. These pro-inflammatory genes remain expressed, even when the HIV protein is no longer in the cells. According to the researchers, this “immunological memory” of the initial HIV infection is why people living with HIV are susceptible to prolonged inflammation, which puts them at increased risk of developing cardiovascular disease and developing cardiovascular disease. other comorbidities.
“This research underscores the importance for physicians and patients to recognize that suppressing or even eliminating HIV does not eliminate the risk of these dangerous comorbidities,” said Michael Bukrinsky.,professor of microbiology, immunology and tropical medicine at the GW School of Medicine and Health Sciences and lead author of the study, said. “Patients and their physicians should always discuss ways to reduce inflammation, and researchers should continue to search for potential therapeutic targets that may reduce inflammation and comorbidities in HIV-infected patients.”
For the study, the research team isolated human immune cells in vitro and exposed them to the HIV Nef protein. The amount of Nef introduced into cells is similar to the amount found in regarding half of HIV-infected people taking antiretrovirals with an undetectable HIV load. After some 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 a high level of inflammatory proteins, called cytokines. When the team compared the genes of cells exposed to Nef with the genes 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 Bukrinsky, the results of this study might help explain why certain comorbidities persist following other viral infections, including COVID-19.
“We’ve seen this pro-inflammatory immunological memory reported with other pathogens and often referred to as ‘trained immunity,'” says Bukrinsky. “While this ‘trained immunity’ has evolved as a beneficial immune process to protect once morest new infections, in some cases it can lead to pathological outcomes. The ultimate effect depends on the duration of this memory, and extended memory may underlie long-lasting inflammatory conditions. as we see in HIV infection or the long COVID.”
The article, “HIV-1 Nef-carrying extracellular vesicles induce long-term myeloid cell hyperresponsiveness,” will be published in Cell reports November 14. The National Institute of Health’s National Heart, Lung and Blood Institute supported this research.
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