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Overview

Zika is caused by a flavivirus similar to dengue virus and is endemic in many of the same tropical and subtropical regions. Zika (and dengue) viruses are transmitted via A. aegypti or A. albopictus mosquitoes, but Zika can also be transmitted sexually in semen and to a fetus during pregnancy. In adults, Zika symptoms can appear quite mild and cause symptoms such as fever, rash, joint and muscle pain and conjunctivitis.

However, infection in fetuses and infants can be devastating. Around 5 to 10 percent of babies born to mothers infected with Zika exhibit catastrophic Zika-associated birth defects, among them microcephaly and Guillain-Barre syndrome, an immune attack on nerves that can cause paralysis. Currently there is no anti-Zika vaccine available.

LJI scientists are making great strides in understanding conundrums related to flaviviruses—how seemingly mild conditions become catastrophic and how immunity to one can trigger reactivity to another. This knowledge is essential in order to engineer a vaccine. LJI scientists have also recently shown that Zika infection could have long-term effects on the brain.

Our Approach

Sujan Shresta, Ph.D., has developed mouse models of Zika virus infection and has used them to monitor immune responses to viral infection, screen vaccine candidates or anti-Zika drugs, and explore a paradoxical cross-reactivity scenario unique to flaviruses known as ADE. In the latter, the presence of antibodies recognizing one flavivirus triggers a lethal inflammatory response to a related flavivirus. In one widely-cited experiment, Shresta showed that newborn mouse pups harboring anti-Zika antibodies were more vulnerable to death from dengue exposure than mice that lacked anti-Zika antibodies (see “dengue” for more about ADE.).

Dr. Shresta’s mouse models also formed the basis for a collaboration with Rockefeller University investigators showing that neural progenitor or “stem” cells in brains of adult mice are targeted by the Zika virus and when infected undergo cell death and decreased proliferation. This suggests that Zika infection may inflict damage on the adult brain in ways that only become apparent years later, such as memory loss or depression.

Alessandro Sette, Dr. Biol. Sci., who is known for his work studying the role of T cells in the immune response to dengue virus, is expanding his interests to Zika and asking whether immune cells activated in prior flavivirus infections can cross-react with Zika virus. He and LJI’s Bjoern Peters, Ph.D., and Pandurangan Vijayanand, M.D., Ph.D., are identifying components of the virus particle most likely to elicit an immune response. Their work was the first to characterize the human CD8+ T cells that respond to Zika infection.

LJI’s research and expertise in Zika and dengue virus infections is already guiding vaccine efforts. Shresta recently piloted a DNA-based anti-Zika vaccine that elicits a protective T cell response in mice. She is now taking this research to the next level by developing a pan-flavivirus vaccine that elicits protective antibody and T cell responses against all four dengue serotypes and Zika. If successful, this approach would circumvent issues related to harmful cross-reactivity between these viruses and represent a major step toward the first universal anti-Zika and anti-dengue vaccine strategy.

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Research Projects

Shresta
Emergence of Mosquito-Borne Viruses Such as DENV and ZIKV in Nepal

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Shresta
Development of Vaccines Against DENV and ZIKV

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Shresta
Adaptive Immune Response to DENV and ZIKV

Vaccine development for DENV is challenging in that the vaccine must induce long-lasting immunity against all four DENV serotypes (DENV1-4),

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Shresta
Innate Immune Response to DENV and ZIKV

The IFN system is a major mechanism by which many viruses evade the cellular antiviral response. DENV and ZIKV can

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More research projects

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Labs

Jul 8, 2020
Shresta Lab

Sujan Shresta, Ph.D., and her team study the immunology and virology of mosquito-borne human pathogens such as dengue virus and Zika virus.

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Sujan Shresta, Ph.D.
Associate Professor
Center for Infectious Disease and Vaccine Research
Jul 2, 2020
Sette Lab

Alessandro Sette, Dr. Biol. Sci., defines in chemical terms the specific structures (epitopes) that the immune system recognizes and uses this knowledge to measure and understand immune responses.

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Alessandro Sette, Dr.Biol.Sci.
Professor
Center for Autoimmunity and Inflammation, Center for Infectious Disease and Vaccine Research