Recent Zika Research Uncovers Pathways to Beat the Virus

Recent studies on Zika have lead researchers to discover how the virus causes neurological complications, as well as ways in which the body can fight off the infection.

Zika is a flavivirus infection transmitted by the Aedes aegypti mosquito, which carries Dengue, West Nile Virus and yellow fever. Zika has been confirmed to cause microcephaly in the fetuses of infected pregnant women. Recently, the World Health Organization (WHO) reported that there is scientific consensus that the virus also causes Guillain-Barré syndrome. Furthermore, not only can the virus be transmitted through vaginal and anal sex from a man to a partner, but a letter recently published in the New England Journal of Medicine cited a case study which confirmed that infection can also be transmitted through oral sex.

In one study, researchers, led by John Schoggins, PhD, assistant professor at the University of Texas Southwestern Medical Center, recently discovered how Zika causes neurological complications. Published in Cell Reports, the study confirms that Zika infects progenitor cells, the cells which develop into neurons. Using the Zika strain currently circulating in the Americas, the researchers found that not only does the virus infect an average of 20% of progenitor cells, it does so without being detected by the immune system, which aids in the prolongation of viral replication. In regards to the research findings, Dr. Schoggins, stated, “We found that the virus kills some neural progenitor cells, but not all. Other cells survive the infection, and surprisingly, continue to replicate the virus for many weeks. In addition, it appears that Zika virus does not stimulate much of an immune response.”

In a second article, published in the same journal, researchers were able to determine a means of combating viral effects. The researchers determined that, using interferon-induced protein 3 (IFITM3), a protein naturally found in all human cells, they can reduce the virus’ ability to infect both human and mouse cells. Additionally, IFITM3 may even be able to prevent the virus’ effects that result in cell die-off.

Senior author, Abraham Brass, MD, PhD, assistant professor of microbiology and physiological systems, commented on the findings by stating, “This work represents the first look at how our cells defend themselves against Zika virus’ attack. Our results show that Zika virus has a weakness that we could potentially exploit to prevent or stop infection.”

By altering cell membranes, IFITM3 disallows the virus from entering the cell. George Savidis, research associate at the Brass lab and first author of the study stated, "In effect, we see that IFITM3 allows our cells to swallow up and quarantine the virus thereby stopping their own infection, and also the infection of neighboring cells."

"We think this also reduces the levels of cell death caused by Zika virus." Savidis elaborated, “This work shows that IFITM3 acts as an early front line defender to prevent Zika virus from getting its hands on all of the resources in our cells that it needs to grow.”

In addition, previous research has uncovered that those individuals that are homozygous for the IFITM3 allele, rs12232-C, are at an increased risk for severe influenza. This allele is more prevalent in individuals from Asia and Micronesia, and given the increasing prevalence of the Zika virus in these regions, the authors are interested in determining if this allele may also be a risk factor for other severe infections in both mothers and fetuses. The authors hope to learn if it also contributes to birth defects associated with the Zika virus.

Dr. Brass, in conjunction with Sharone Green, MD, associate professor of medicine, and a flavivirus expert, will be testing these findings on IFITM3-deficient mice, in an effort to analyze animal susceptibility in comparison to human susceptibility. Furthermore, studies are being conducted to find molecules that can increase IFITM3 levels and their anti-viral effects, which Dr. Brass believes can be incorporated into therapies and vaccines for not only Zika, but other viruses as well. He confirms that IFITM3 can block many viruses in addition to Zika, such as Dengue and Ebola. He states, “Given our recent results with Zika virus, it’s now even more important that we work to find out how IFITM3 is blocking these viruses, and use that knowledge to prevent and treat infections.”

The findings from these two studies can help advance future therapy and vaccine efforts. Not only is it now known how the virus causes microcephaly and other neurological disorders, but the means of combating infection have also been discovered. Although most individuals infected with the virus are either asymptomatic or present with mild symptoms, infection in a pregnant woman can have tragic consequences.

In a recent blog post on the White House website, Tom Frieden, MD, MPH, director of the Centers for Disease Control and Prevention (CDC), expresses the urgency with which he believes Zika should be dealt with. He states, “Doctors who have spent the past three decades working in CDC’s birth defects center tell me that they have never seen a situation so urgent. The ability to prevent dozens, hundreds, or even thousands of severe birth defects creates a special responsibility — every child protected is a tragedy prevented.”

Although Congress has yet to grant Zika funding, the CDC has utilized its non-profit foundation to build partnerships with private sectors and philanthropic organizations. Thus far, those organizations and companies which participated in this partnership have supported the CDC Foundation in several ways, including donating prevention equipment, such as mosquito nets and contraceptives, participating in collaborative efforts to disseminate Zika-prevention kits in Puerto Rico, and supporting health campaigns to educate communities on the Zika virus.