From Viral Storms to Immune Checkpoints: Decoding How the Body Battles Infection

When a virus enters our body, the immune system must make rapid decisions. It has to attack strongly enough to control the infection, but not so aggressively that it harms our own tissues. Immune receptors play a central role in making these decisions. They act like molecular sensors, detecting danger and directing immune responses.

But these same receptors can sometimes be pushed in the wrong direction. Some viruses exploit them to hide from the immune system. In other cases, the receptors trigger an excessive inflammatory response, causing blood clots, organ injury, or long-term infection.

At the School of Pharmacy, Taipei Medical University (TMU), Dr. Pei-Shan Sung investigates how innate immune receptors—particularly C-type lectins and Siglecs—shape the outcome of viral infections. Her research bridges fundamental immunology with therapeutic development, advancing new strategies to combat both acute viral crises and chronic persistent infections.

Dr. Sung’s work has revealed unexpected roles for platelets beyond blood clotting. Her research demonstrated that during Dengue virus and SARS-CoV-2 infections, activated platelets release extracellular vesicles that trigger excessive inflammation through CLEC5A and TLR2 receptors—a process known as thromboinflammation. These discoveries, published in Nature Communications (2019) and Journal of Biomedical Science (2022), helped explain how some viral infections cause life-threatening blood clots and organ failure. In a subsequent study published in EMBO Molecular Medicine (2023), Dr. Sung further identified the platelet receptor CLEC2 as a potential therapeutic target in SARS-CoV-2-mediated thromboinflammation. Blocking this pathway with an engineered fusion protein (CLEC2.Fc) significantly reduced lung damage and systemic inflammation in preclinical models. Crucially, Dr. Sung identified potential therapeutic targets within this pathway: blocking the platelet receptor CLEC2 with an engineered fusion protein (CLEC2.Fc) significantly reduced lung damage and systemic inflammation in preclinical models. These findings now form the foundation for her independent research program at TMU, with ongoing efforts to develop this approach for clinical translation.

Building on these insights into immune regulation, Dr. Sung is now tackling one of the most persistent public health challenges in Taiwan and across Asia: Chronic Hepatitis B (CHB), which affects over 250 million people worldwide. Her research focuses on CD33 (Siglec-3), an inhibitory receptor that normally acts as an immune checkpoint to restrain excessive immune activation. A study published in the Journal of Clinical Investigation (2021) revealed that hepatitis B virus exploits CD33 to suppress antiviral immunity, allowing the virus to persist for decades. At TMU, Dr. Sung’s laboratory is employing single-cell genomics and patient-derived samples to investigate how CD33-positive immune cells contribute to viral persistence and whether targeting this pathway—similar to cancer immunotherapy approaches that block PD-1—could restore effective antiviral responses. This work is supported by the National Science and Technology
Council’s prestigious 2030 Cross-Generation Young Scholars Program, which holds direct translational potential toward achieving a “functional cure” that would allow patients to discontinue lifelong antiviral treatment.

Dr. Sung’s research exemplifies translational immunology: discovering fundamental mechanisms of host-pathogen interactions and translating them into therapeutic strategies. Her work on C-type lectins has progressed from basic discovery to patent-protected biologics, while her CD33 research is revealing new immunotherapy targets for chronic viral infections. At TMU, she is establishing a research program that combines cutting-edge technologies—single-cell genomics and antibody engineering—with clinically relevant questions. Her vision is to transform the understanding of immune receptors into precision medicines, positioning TMU at the forefront of translational immunology research.

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Original Articles:

1. Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2
2. SIGLEC-3 (CD33) serves as an immune checkpoint receptor for HBV infection
3. CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation
4. Inhibition of SARS-CoV-2-mediated thromboinflammation by CLEC2.Fc

Author Profile:

Pei-Shan Sung, Assistant Professor, School of Pharmacy, College of Pharmacy