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When people living with HIV take antiviral therapy, their viral loads are driven so low that a standard blood test cannot detect the virus. However, once the therapy is stopped, detectable HIV re-emerges with new cells getting infected.
This is called “rebound” virus and comes from a population of cells in blood and lymph tissues that were dormant while individuals were on therapy.
It’s a problem called latency, and overcoming it remains a major goal for researchers trying to create curative therapies for HIV — the special focus of the UNC HIV Cure Center.
Now, scientists led by virologist Ron Swanstrom, PhD, director of the UNC Center for AIDS Research and the Charles P. Postelle, Jr. Distinguished Professor of Biochemistry & Biophysics at the UNC School of Medicine, have discovered another layer to the challenge of HIV latency.
Swanstrom and colleagues, with collaborators at UCSF, Yale and the University of Gothenburg in Sweden, have found indirect evidence for a new reservoir of latent HIV-positive cells in the central nervous system.
By studying cerebral spinal fluid in patients who had just quit antiviral therapy, researchers found that dormant infected cells in the central nervous system are separate to infected cells in the already known reservoir in the blood.
The upshot: Any curative therapy to treat HIV would need to activate this dormant reservoir in the central nervous system, as well as the reservoir in the blood and lymph tissue.
The viruses Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) have been linked to several cancers.
For the first time, UNC School of Medicine scientists have discovered that these viruses use a human protein called barrier-to-autointegration factor 1, or BAF, to evade our innate immune response, allowing the viruses to spread and cause disease.
These findings suggest that BAF and related proteins could be therapeutic targets to prevent these viruses from spreading and leading to cancers, such as Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, multicentric Castleman disease, nasopharyngeal carcinoma and gastric cancer.
“Viruses are in a constant battle with the cellular immune system, which includes the protein cyclic GMP-AMP synthase — cGAS — which binds to viral DNA and sounds the alarm to trigger immune responses and fight the viral invaders,” said senior author Blossom Damania, PhD, the Boshamer Distinguished Professor of Microbiology and Immunology and member of the Lineberger Comprehensive Cancer Center. “We’ve discovered that KSHV and EBV use a different host cell protein, BAF, to prevent cGAS from sounding the alarm.”
First author Grant Broussard, a graduate student in the Genetics and Molecular Biology Curriculum at UNC Lineberger said, “Our study highlights the prominent role that DNA detection pathways like the cGAS pathway play in controlling viral infection.”
“We knew that we had done something amazing scientifically.”
That’s what Eva Telzer, co-director of Carolina’s Winston National Center on Technology Use, Brain and Psychological Development, said about the moment in late 2022, when the center’s research team analyzed results from the first-ever study linking teens’ habitual checking of social media to changes in their brains’ development.
Doctoral students Kara Fox and Maria Maza, the study’s primary authors, are part of the center’s team that leads a fairly new research field — the role of technology and social media on adolescent brain development. They’re already helping people — parents and teens, especially — who are concerned about the effects of screen time.
The Journal of American Medical Association Pediatrics published the findings in January 2023. By then, a $10 million gift in March 2022 from the Winston Family Foundation had expanded the team’s work by creating the center.
The center is not only working on research studies. It is also training students for scientific careers and disseminating videos on how digital media can affect children and adolescents.
“We’re just getting started,” Telzer said. “We plan to do a lot more. We hope to expand our curriculum to younger ages and continue our dissemination, getting the science out there and helping people to understand why what we study is so important.”
