- A desire to help her home country by fighting infectious diseases fuels Dr. Sujan Shresta’s work with killer T-cells
- When antibodies are not strong enough to fight Zika, killer T-cells step in to help
- The link between the Zika virus and Dengue fever connects their vaccines
Dr. Sujan Shresta, PhD, is an associate professor at the Center for Infectious Disease at the La Jolla Institute for Allergy and Immunology. Growing up in Nepal, Dr. Shresta always knew she wanted to give back to her country. As a researcher, Dr. Shresta now fulfills this goal by working to eradicate the Zika virus and the Dengue fever, which plague Nepal and many other developing countries. “My contribution to the field has really been trying to convince [everyone] that T-cells are important in mediating protection and we think that vaccines for these viruses should elicit antibody T-cell responses,” says Dr. Shresta.
Using T-cells in addition to antibodies is a fairly unexplored approach. Killer T-cells are white blood cells that can kill infected cells or call other immune cells to destroy unwanted pathogens in the body. “[There are] two arms of the immune system in case one is not sufficient. So if the antibody response is not good enough to protect [the body], you have the T-cell response and vice versa.” says Dr. Shresta.
The first “arm” of the immune system is antibody-dependent enhancement, or ADE, and allows the antibody response to be positive or negative. If the response is negative, the antibodies allow viruses to enter the cell and the viral infection becomes significantly worse. As Dr. Shresta says, “You need teamwork, instead of just relying on half a team.” After the antibody cells are controlled by the virus, the second arm of the immune system, killer T-cells, take over the antibodies’ job and decrease the severity of the infection.
Dr. Shresta and her team used CD8+ T-cells to see if these cells had a powerful response to Zika and they did. CD8+ T-cells, also known as cytotoxic T-cells, are white blood cells specialized to kill cancer cells, damaged cells, and infected cells. This research gave Dr. Shresta’s team a starting point, allowing them to learn more about the Zika virus and its response.
Since this viral infection is so complicated, Dr. Shresta and her team tried to find similarities with another virus to see if it would give them more information. Transmitted through the same type of mosquito, Dengue fever and the Zika virus are very similar. “All the places that the Zika virus is found are Dengue-infected countries,” says Dr. Shresta.
In these infected countries, many doctors find it difficult to diagnose Zika due to its similarity to Dengue. The increase in Zika in these Dengue-infected countries has led Dr. Shresta and her team to realize that these two viruses are cross-reactive. Cross-reactivity means that “the antibodies for Dengue will recognize not only Dengue, but will also recognize Zika and they can have either a positive or negative [antibody] effect depending on the quality of the antibody response,” explains Dr. Shresta. This cross-reactivity makes vaccine development more difficult because scientists must consider antibodies and T-cell responses for both viral infections.
Despite that, with the help of Dr. Shresta, her team, and the fact that the Dengue fever and the Zika virus are so similar, there is hope that a vaccine for both may be attainable in the near future.
Dr. Sujan Shresta is an Associate Professor in the Division of Inflammation Biology at the La Jolla Institute for Allergy and Immunology. Dr. Shresta studies the immunology and virology of the Dengue and Zika virus and their connection to viral immunopathogenesis.
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