Studying T-Cell Response May Help the Fight Against Zika Virus

Since being identified as the cause of widespread infection in Brazil in 2015, the Zika virus has perplexed many researchers. Not only was a virus previously harmless to humans causing life-changing neurological complications, but it also challenged scientists in learning how or why it was causing these complications. Since then, research on the viral characteristics of Zika has come a long way.

Numerous studies have confirmed that the Zika virus causes neurological complications in developing fetuses that are congenitally infected, and more evidence to support these cases continues to come to light. According to a study, to be presented at the 37th Annual Pregnancy Meeting in Las Vegas, Nevada, this week, fetuses that were congenitally infected with the Zika virus in Barranquilla, Colombia during a recent outbreak, developed similar complications to those previously identified in Brazil. At 29 weeks of gestations, the brain tissue of these fetuses had not developed appropriately and the upper part of the brain had abnormal fluid levels.

In an additional study, researchers from La Jolla Institute for Allergy and Immunology, set out to further understand how the Zika virus “interacts with its host” and causes infections. The researchers conducted studies that aimed to think outside the box, or in this case, the antibody. In their study, the team focused on tracking CD8+ T-cells, which they mention are also known as cytotoxic or killer T-cells. They found that these T-cells may control the severity of infection within a Zika-infected individual.

Sujan Shresta, PhD, associate professor at the Center for Infectious Disease at La Jolla Institute, and senior study author, stated in a press release, “Our study acknowledges the importance of T-cells in an environment where most people are focused on antibodies… For most diseases a strong antibody response is enough. But with Zika and Dengue viruses a phenomenon known as antibody-dependent enhancement is a concern, which makes a strong T-cell response really important.”

Expanding on antibody response to infection with other viruses, the researchers noted that those infected with influenza are able to fight off different strains of the virus more easily because their bodies produce virus-specific antibodies for a similar strain of the flu; however, this is not the case for those who were previously infected with one of the four Dengue serotypes. Because the Zika virus is closely related to the Dengue virus, the researchers believed that antibody response during infection with the Zika virus may be similar to that which occurs during Dengue infection. In addition, during infection with the Dengue virus, T-cells were found to play an important role, and, due to similarities between the two viruses, the research team set out to identify the role of T-cells during Zika virus infection.

By blocking the interferon 1 receptor in mice, Annie Elong Ngono, PhD, first author of the study, was able to infect the mice with the Zika virus. She then went on to identify “which portions of the virus elicited a strong immune response,” by examining T-cells from these mice. Dr. Ngono repeated this experiment in mice that were T-cell competent and discovered that “both mouse models mount a robust CD8+ T-cell response to Zika infection.” Ultimately, the researchers hypothesize that CD8+ T-cells may play a role to protect against flaviviruses other than the Zika virus.

In addition, these findings provide an opportunity for scientists to identify how the virus is able to be transmitted through tears, saliva, and semen, according to the press release. The researchers believe that this study’s findings will also allow for the identification of additional pathways through which Zika causes neurological complications, such as Guillain-Barré syndrome.

Commenting on the findings, Dr. Ngono stated, “Being able to track Zika-specific T-cells across different model systems provides a valuable tool to better understand sexual and trans-placental transmission and how the virus crosses the blood-brain barrier and reaches other immune-privileged areas such as testes and the eye.”

With this research, we are one step closer to understanding how the Zika virus infects its hosts; however, we still have a long way to go. Researchers have identified several modes of viral transmission, including vaginal and anal intercourse, blood transfusions, and even tears. However, it seems that we still do not fully understand all there is to know about Zika virus transmission. In fact, in July 2016, Utah health officials announced that a patient in Salt Lake City who had recently died was, in fact, infected with the Zika virus. This became the first Zika-related death in the United States. Zika virus infection was later confirmed in a relative who had no history of recent travel to a Zika-endemic region or other reportable mode of transmission other than direct contact with the deceased. According to a Utah Department of Health (DOH) news release on January 17, 2017, there are no Zika-infected mosquitoes within the area where the second patient resides. The DOH reports that this is not a closed case and that other departments within the state are “keeping an eye on the situation.”