Researchers at the University of Massachusetts Medical School (UMMS) say they have found that interferon-induced protein 3 (IFITM3) can dramatically reduce the ability of Zika virus to infect human and mouse cells. In some cases, IFITM3 can also prevent Zika virus from killing our cells.
The findings, by senior author Abraham Brass, M.D., Ph.D., assistant professor of microbiology and physiological systems, suggest that boosting the actions of IFITM3 may be useful for inhibiting Zika virus and other emerging viral infections. The study (“The IFITMs Inhibit Zika Virus Replication”) appears in Cell Reports.
“This work represents the first look at how our cells defend themselves against Zika virus' attack,” said Dr. Brass. “Our results show that Zika virus has a weakness that we could potentially exploit to prevent or stop infection.”
Previous studies by Dr. Brass and Paul Kellam, Ph.D., a professor from the Wellcome Trust Sanger Institute in the U.K., have demonstrated that people who have a genetic variant of the IFITM3 gene are more susceptible to the development of severe influenza. While relatively rare in people of European descent, this IFITM3 variant is more common in Asia and Micronesia. The current study suggests that it will be important to test whether this allele might contribute to the risk of more severe Zika virus infections and birth defects, according to Dr. Brass, who has developed a suite of genomic tools to probe how human cells respond to pathogens and how these invaders exploit host cell factors and proteins to replicate.
“Having these tools allowed us to respond quickly when the Zika virus threat emerged,” noted Dr. Brass. “We simply adapted the technology we'd developed over the last 4 years working with dengue, influenza, and other viruses to begin work on Zika virus.
“We just plugged Zika virus into our system and immediately began testing it. What might have taken many months or longer to build, we were able to turn around in just several weeks.”
Found in nearly all human cells, IFITM3 works to alter the cell membrane, making it more difficult for viruses to penetrate this outer defense. The Brass lab found that when IFITM3 levels are low, Zika virus can more readily infiltrate into the cell interior and cause infection. Conversely, they discovered that when IFITM3 is abundant and on guard, it strongly prevents Zika virus from reaching the interior of the cell and so blocks its infection.
The next step for Brass and his collaborators, including Sharone Green, M.D., associate professor of medicine and a flavivirus expert at UMMS, is to test these findings in mice that are IFITM3-deficient to see whether these animals are more susceptible to the effects of Zika virus infection. The Brass lab is also searching for small molecules that can boost the levels, and hopefully the antiviral actions, of IFITM3. Dr. Brass believes that such molecules could be developed into therapies to treat or protect us from Zika virus, as well as a growing list of other dangerous viruses.