HIV-1 proviruses may drive chronic systemic inflammation

HIV (human immunodeficiency virus) is a virus that attacks the body’s immune system and remains a major global health challenge because of persistent viral reservoirs, despite effective treatments. Key factors include around 40 million people living with HIV, 1 million new infections each year and permanent viral DNA integration into host cells. Some HIV proviruses hide quietly in cells and escape both medicines and the immune system, creating a permanent viral reservoir that prevents patients from being cured.

People living with HIV are at higher risk of developing inflammatory diseases in many tissues, including the brain, heart, intestine and immune tissues, even when receiving antiviral treatments that control HIV expression and spread. A new study by researchers at Boston University Chobanian & Avedisian School of Medicine suggests that persistent hidden HIV contributes to this inflammation. The work is published in the Journal of Virology.

“People with HIV-1 are at higher risk of developing age-associated comorbidities and immune exhaustion even when receiving antiviral treatments and having no detectable virus present in the blood. Our results highlight the importance of the persistent defective HIV-1 proviruses and understanding their impact on driving chronic inflammation to inform future strategies to ensure healthy living and aging for people with HIV-1,” said corresponding author Andrew Henderson, Ph.D., professor of medicine and virology, immunology & microbiology.

For this study, the researchers infected cells and generated cells with defective viruses using the editing tool CRISPR (clustered regularly interspaced short palindromic repeats), or molecular scissors, to prevent them from normally expressing HIV. They then compared cells with HIV with cells with defective HIV and measured markers of inflammation. An increase in inflammation markers was observed in the cells with the modified viruses.

According to the researchers, these findings could have implications for the persistent inflammation observed in people with HIV, especially as this population lives longer. “It may also provide some general mechanisms that contribute to persistent inflammation associated with autoimmunity or aging.”

The researchers believe the study also provides additional insights into how HIV leads to general immune dysfunction and has potential implications for HIV cure strategies and targeting the persistent HIV reservoir.

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Gaby Clark

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Robert Egan

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