How dengue virus activates human microglial cells?

January 13, 2021

Dr. Ritu Mishra completed her Ph.D. from CCMB, Hyderabad, and pursued postdoctoral research at the Max Planck Institute of Molecular Biomedicine, Germany. She is currently working as a DST-INSPIRE Faculty at the National Institute of Immunology, New Delhi. Her expertise lies in virology, immunology, and neurological research, with extensive work on HIV, Dengue, JEV, and SARS-CoV-2 viruses. She is the first author of the paper titled “Dengue Virus Degrades USP33–ATF3 Axis via Extracellular Vesicles to Activate Human Microglial Cells” published in The Journal of Immunology (2020).

Author Interview

How would you explain your paper’s key results to the non-scientific community?

Many viruses that infect a specific organ can indirectly influence the health of other organs. For example, during the COVID-19 pandemic, although the coronavirus primarily infects the lungs, it also affects the brain, gut, and heart.

Our research demonstrates how Dengue virus can affect the brain even after the patient has recovered. This happens through viral proteins and host molecules (like miR-148a) that remain in the plasma. These are packaged into tiny carriers called extracellular vesicles or exosomes.

These exosomes are absorbed by microglia, the immune cells of the brain. Inside microglia, a molecule called miR-148a disrupts the USP33–ATF3 pathway, which normally helps suppress brain inflammation. Disruption of this pathway results in a cytokine storm, leading to neuroinflammation, a condition that can damage brain function.

Our work provides a novel insight into how exosomes from viral infections contribute to multi-organ dysfunctions, especially in the brain.

What are the possible consequences of these findings for your research area?

Our findings provide deeper insights into why some patients suffer from multi-organ issues even after recovering from Dengue. This is also relevant for “Long COVID” cases where patients experience heart, kidney, or neurological symptoms post-recovery.

This work also raises concerns about Plasma Therapy in COVID-19. Plasma from recovered patients may contain inflammation-triggering molecules. Its unfiltered use might worsen a patient’s condition by fueling a cytokine storm. Hence, our study serves as a caution for such treatments.

What was the exciting moment (eureka moment) during your research?

In science, eureka moments occur when hypotheses are validated by experimental data. In this project, we experienced several such moments—especially when new pathways and mechanisms revealed themselves through our cellular and animal models. These discoveries were truly exhilarating.

What do you hope to do next?

I have been deeply involved in studying how viral infections impact the human brain—ranging from HIV-1 to JEV, Dengue, and now SARS-CoV-2. So far, we have relied on cell cultures and animal models. My next step is to shift toward 3D human brain organoids or “mini-brains.”

These organoids mimic real brain tissue and offer an excellent system to explore how viruses cause neurological issues. I plan to use them to investigate disease mechanisms and also for drug testing and repurposing—aiming to find therapeutic solutions against neuro-viral infections and neuroinflammation.

Where do you seek scientific inspiration?

I find inspiration in the pursuit of unanswered questions, especially around neuro-viral infections and brain dysfunction. My mind constantly seeks to connect the dots between various observations, drawing a bigger picture of human disease mechanisms.

This innate curiosity keeps driving me to dig deeper into the mysteries of the brain and its interactions with viral pathogens.

How do you intend to help Indian science improve?

While government funding is crucial, what we truly need is systemic support—centralized facilities, timely access to instruments, and a supportive infrastructure.

But more importantly, we need early scientific sensitization. Education in India is often pursued for livelihood, not personal growth. In science, this mindset is limiting.

We must encourage students from a young age to follow their passion and pursue education with joy and purpose. I aim to contribute by balancing my research with science communication and teaching, inspiring the next generation to value science as a way of thinking and living.

Reference

Ritu Mishra, Anismrita Lahon, Akhil C. Banerjea. Dengue Virus Degrades USP33–ATF3 Axis via Extracellular Vesicles to Activate Human Microglial Cells. The Journal of Immunology, 2020, 205(7): 1787–1798.

Author Introduction and Research Interests

Dr. Ritu Mishra is a DST-INSPIRE Faculty at the National Institute of Immunology, New Delhi. She has expertise in virology, immunology, and neurobiology, with research spanning HIV, Dengue, JEV, and SARS-CoV-2. She is passionate about understanding how viruses affect the human brain and aims to discover new therapeutic strategies using advanced human brain organoid models.