Study: HIV Infection Leaves ‘Memory’ in Cells, Resulting in Persistent Comorbidities

New research has found that HIV infection leaves a “memory” in cells, which helps explain why patients often struggle with chronic inflammation and comorbidities, such as cardiovascular disease and neurocognitive dysfunction.

Antiretroviral therapies have made HIV a manageable disease, but patients living with it often have ongoing inflammation and associated comorbidities. In the study, investigators from George Washington University demonstrated how an HIV protein permanently alters immune cells, causing them to overreact to other pathogens.

When the protein is introduced to immune cells, genes in those cells associated with inflammation become expressed. These pro-inflammatory genes remain expressed even when the HIV protein is no longer in the cells. This “immunologic memory” of HIV explained why individuals with HIV are susceptible to prolonged inflammation.

“This research highlights the importance of physicians and patients recognizing that suppressing or even eliminating HIV does not eliminate the risk of these dangerous comorbidities,” said lead author Michael Bukrinsky, MD, PhD, in a press release. “Patients and their doctors should still discuss ways to reduce inflammation and researchers should continue pursuing potential therapeutic targets that can reduce inflammation and comorbidities in HIV-infected patients.”

In the study, the research team isolated human immune cells in vitro and exposed them to the HIV protein Nef. The amount of Nef introduced to the cells is similar to the amount found in about half of HIV-infected individuals taking antiretrovirals whose HIV load is undetectable. After a period of time, the researchers introduced a bacterial toxin to generate an immune response from the Nef-exposed cells.

Compared to cells that were not exposed to the HIV protein, the study found that the Nef-exposed cells produced an elevated level of cytokines. When the team compared the genes of the Nef-exposed cells with the genes of the cells not exposed to Nef, they identified pro-inflammatory genes that were in a ready-to-be-expressed status as a result of the Nef exposure.

Importantly, the findings could also help explain why certain comorbidities persist following other viral infections, including COVID-19, according to the study authors.

“We’ve seen this pro-inflammatory immunologic memory reported with other pathogenic agents and often referred to as ‘trained immunity,’” Bukrinsky said in the press release. “While this ‘trained immunity’ evolved as a beneficial immune process to protect against new infections, in certain cases it may lead to pathological outcomes. The ultimate effect depends on the length of this memory, and extended memory may underlie long-lived inflammatory conditions like we see in HIV infection or long COVID.”

REFERENCE

HIV Infection Leaves a ‘Memory’ in Cells. News release. George Washington University; November 22, 2022. Accessed November 30, 2022. https://mediarelations.gwu.edu/hiv-infection-leaves-memory-cells