HIV infection leaves a "memory" in cells

While antiretroviral therapy has made HIV a manageable disease, people living with HIV often suffer from chronic inflammation
.
This may increase their risk of comorbidities such as cardiovascular disease and neurocognitive dysfunction, affecting their longevity and quality of life
.
Now, a new study published in Cell Reports explains why chronic inflammation occurs and how suppressing or even eliminating HIV from the body can't solve it
.

In the study, researchers from George Washington University showed how an HIV protein permanently alters immune cells, causing them to overreact to
other pathogens.
Studies have shown that when this protein is introduced into immune cells, genes associated with inflammation are activated or expressed in those cells
.
These pro-inflammatory genes are still expressed
even though HIV proteins are no longer present in cells.
According to the researchers, this "immune memory" of initial HIV infection is why HIV carriers are prone to prolonged inflammation, making them more susceptible to cardiovascular disease and other comorbidities
.

Michael Bukrinsky, professor of microbiology, immunology and tropical medicine at George Washington University School of Medicine and Health Sciences and lead author of the study, said: "This study underscores the importance for
physicians and patients to recognize that suppressing or even eliminating HIV does not eliminate the risk of these dangerous comorbidities.
Patients and their doctors should still discuss ways to reduce inflammation, and researchers should continue to look for potential therapeutic targets that can reduce inflammation and concomitant diseases
in HIV-infected patients.
”

In this study, the team isolated human immune cells in vitro and exposed them to
the HIV protein Nef.
The amount of Nef introduced into the cells is similar to that found in about half of people living with HIV taking antiretroviral drugs, whose HIV load is undetectable
.
After some time, the researchers introduced a bacterial toxin that caused Nef-exposed cells to develop an immune response
.
Compared to cells not exposed to the HIV protein, cells exposed to Nef produced higher levels of inflammatory proteins called cytokines
.
When the team compared the genes of cells exposed to Nef to those of cells not exposed to Nef, they found pro-inflammatory genes
that were in a ready-to-express state due to exposure to Nef.

The study's findings may help explain why certain comorbidities persist after other viral infections, including COVID-19
, said.

"We've seen this pro-inflammatory immune memory reported along with other pathogenic agents, often referred to as 'training immunity,'" Bukrinsky explains
.
"While this 'trained immunity' evolved into a beneficial immune process to prevent new infections, in some cases it can lead to pathological outcomes
.
The ultimate effect depends on the length of this memory, and prolonged memories can be the basis of a long-term inflammatory state, as we see with HIV infection or prolonged COVID
.
”

Extracellular vesicles carrying HIV-1 Nef induce long-term hyperreactivity of myeloid cells