CLIC/GEEC Pathway Drives HIV Particle Uptake in Macrophages
Research By: Paul Spearman, MD
Post Date: March 11, 2025 | Publish Date: March 11, 2025
Infectious Diseases | Top Scientific Achievement
New insights from experts at Cincinnati Children’s may help unlock the virus-containing compartments (VCCs) that the HIV-1 virus builds inside macrophages to hide from the body’s natural immune response and from medication cocktails.
Findings published in March 2025 in PLOS Pathogens detail how the CLIC/GEEC endocytic pathway regulates the internalization of HIV-1 particles in macrophages, leading to the formation of the virus-containing compartment. Kathleen Candor, PhD, was first author and Paul Spearman, MD, was corresponding author.
“This discovery sheds light on a previously unrecognized mechanism by which HIV exploits macrophages, opening new avenues for therapeutic intervention to block viral spread and persistence,” Spearman says.
The study addresses several puzzling aspects of VCC formation, which act as critical sites for viral assembly and facilitate the trans-infection of CD4+ T cells. In tests involving infected macrophages colonized from human blood samples, the team found that Siglec-1, a cell surface receptor, is essential for capturing HIV-1 particles and initiating their journey into the VCC. This process requires dynamin-2 and involves classical CLIC/GEEC markers CD98 and CD44.
Inhibiting this pathway in the lab halted VCC formation and significantly reduced the efficiency of HIV transmission from macrophages to T cells. Next steps include translating these findings into clinical approaches for HIV cure efforts. The researchers also plan to assess the pathway’s role in other viral infections.
About the study
Cincinnati Children’s co-authors also include Lingmei Ding, PhD, Sai Balchand, PhD, and Jason Hammonds, PhD. The Cincinnati Children’s Bio-imaging and Analysis Facility and Research Flow Cytometry Facility also contributed to the work. The study was funded by the National Institute on Drug Abuse (R01 DA051895).
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| Original title: | The CLIC/GEEC pathway regulates particle uptake and formation of the virus-containing compartment (VCC) in HIV-1-infected macrophages |
| Published in: | PLOS Pathogens |
| Publish date: | March 11, 2025 |
Research By
I direct vaccine trials for adults and children, and my research interests extend to HIV, Ebola, SARS-CoV-2 and other pathogens. My team and I are currently developing virus-like particle vaccines for Ebola, HIV and SARS-CoV-2.
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The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment. Email researchnews@cchmc.org with questions or ideas.
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