Study reveals how a specific immune cell may contribute to HIV persistence

Study reveals how a specific immune cell may contribute to HIV persistence

Researchers at the Institute of Human Virology (IHV) at the University of Maryland School of Medicine have discovered how a specific type of immune cell may contribute to the persistence of HIV infections. The finding offers new insight into why the virus remains difficult to cure, even with effective antiretroviral therapy.

The study was published earlier this monthScientific translational medicine. It was led by Guangming Li, PhD, and Lishan Su, PhD, professor of pharmacology at UMSOM and director of the Division of Virology, Pathogenesis and Cancer and interim director of the Division of Immunotherapy at IHV.

The researchers focused on plasmacytoid dendritic cells (pDCs) – a rare immune cell type that is crucial for the body's early defense against viruses. During chronic HIV infection, these cells become overactivated, leading to persistent immune inflammation. This constant activation weakens virus-fighting T cells and allows HIV to remain in hidden reservoirs.

Using humanized mouse models and blood samples from people with HIV, the team found that reducing overactive pDCs helped restore antiviral T cell function and shrink the viral reservoir. When this approach was combined with an immune checkpoint inhibitor—a therapy that revitalizes exhausted immune cells—the immune response improved even further.

Why this research is important

The results show that although the pDC-interferon pathway is essential for antiviral defense, its overactivation can weaken the immune control of HIV. This helps explain why immune inflammation in people with HIV persists despite treatment and why a cure remains elusive.

This study represents our decade-long effort to understand the complex role of pDCs in HIV-associated diseases. Our research shows that the immune system's sustained efforts to fight infection can sometimes work against itself. By reorienting this system, we may be able to open up new avenues for therapy.”

Lishan Su, PhD, Professor of Pharmacology, UMSOM

While the majority of the study was conducted in laboratory and animal models, key observations were confirmed in blood samples from people living with HIV.

“Future studies will clarify whether temporary adaptation of these immune cells can safely improve immune balance and contribute to HIV healing strategies,” said Dr. Li.

This research builds on UMSOM and IHV's long-standing commitment to advance HIV biology and develop new therapeutic strategies.

Mr. Yaoxian Lou, doctoral student in microbiology and immunology at UMSOM, Dr. Shyamasundaran Kottilil and Poonam Mathur from IHV/UMSOM are co-authors of the manuscript. Additional co-authors of the study include researchers from the University of North Carolina at Chapel Hill and Weill Cornell Medicine. The study was supported by grants from the NIH (AI136990, CA298839), the National Cancer Institute Cancer Center Support Grant (P30CA134274), and a grant from the University of Maryland School of Medicine (1UL1TR003098).

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