Zika

The current Zika outbreak has been declared an international health emergency by the World Health Organization citing concerns that as many as four million people could be infected by the end of 2016.

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.

FACULTY MEMBERS

Bjoern Peters, Ph.D.
Alessandro Sette, Dr. Biol.Sci.
Sujan Shresta, Ph.D.

From The Lab

Jun 4, 2020

Fighting Mosquito-Borne Viruses Requires a Precise Balance of Immune Cells

Future vaccines will need to harness the power of T cells in preventing Zika fever and Japanese encephalitis
Nov 14, 2018 // NOVA PBS

How Zika and Dengue Exploit the Mother-Child Relationship

Due to the similarities between these closely-related viruses, mothers who have experienced Zika infections may have babies with a higher risk of suffering severe dengue, and vice versa.
Nov 14, 2018 // Cell Host & Microbe

Maternally-acquired Zika immunity can increase dengue disease severity in mouse pups

The study is highly relevant for infants born in regions where both dengue and Zika virus are endemic
Nov 13, 2018 // Journal of Immunology

Global immunoprofiling effort reveals multifunctional T cell response during Zika infection

Results establish a benchmark for a protective immune response against the virus, providing a guide for Zika vaccine development
Aug 2, 2018 // Nature Communications

Maternal dengue immunity protects against fetal damage in mice following Zika virus infection

Cytotoxic T-cells mobilized by dengue infection may combat catastrophic effects of Zika infection