A multidisciplinary team at Yale University School of Medicine have created a mouse model for vaginal Zika virus infection.
Contrary to concerns expressed by public health experts earlier this year, the ongoing outbreak of Zika virus in Brazil failed to impact the 2016 Summer Olympics held in Rio earlier this month.
However, the virus is very much still a top-of-mind issue for health officials globally, particularly as at least 43 localized cases have been identified in South Florida, and the US National Institutes of Health has warned that recent flooding in Louisiana could lead to significant standing water in the region, creating the perfect breeding ground for the Aedes aegypti mosquito, which carries Zika.
Thankfully, researchers are continuing to glean new insights with regard to virus transmission, and this knowledge could shape the development of preventive strategies, including, possibly, a vaccine against Zika. In a key study, published in the journal Cell on August 25, a multidisciplinary team at Yale University School of Medicine have created a mouse model for vaginal Zika virus infection. The finding is significant, as Zika is transmitted from person-to-person via sexual contact.
Using their previous experience with mouse models for genital herpes, the Yale team vaginally infected otherwise healthy, pregnant mice with Zika, and found that the virus can survive and replicate in the mucosa for several days. The discovery is particularly remarkable, given that mice aren’t normally susceptible to Zika. Their work is the first to prove conclusively that vaginal mucosa is a site for Zika virus replication.
“Our study showed that Zika virus can replicate in the vaginal tract and persist for an extended period of time in mice with intact immune responses,” study co-author Akiko Iwasaki, PhD, Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellular and Developmental Biology at Yale told Contagion. “In pregnant mice, vaginal Zika infection resulted in not only local replication but also infection of the fetal brain, as well as growth restriction of the fetus when the mother was challenged early during pregnancy.”
The authors reached several other important conclusions. In study mice, they found that innate RNA sensors and type I interferons controlled vaginal Zika virus replication, and that vaginal Zika virus infection of pregnant dams leads to fetal brain infection—an important finding, given that microcephaly in babies born to pregnant mothers infected with Zika has been relatively common. Indeed, in the mice they genetically engineered to be vulnerable to Zika, Dr. Iwasaki and her team observed slowed development and brain infection in the fetuses. In fact, the virus replicated uncontrollably in the fetus and caused spontaneous abortions.
“In all cases, our study showed the importance of viral sensors and the interferon system in blocking viral spread,” Dr. Iwasaki added.
According to Dr. Iwasaki, the new mouse models will potentially enable researchers to generate answers to important questions surrounding Zika, such as: Does vaginal Zika transmission cause similar diseases in the infected female or in the developing fetus? And, what are the consequences of Zika infection long term, and can the virus replication in the female genital tract be blocked? Dr. Iwasaki and her team are already working on research into these questions as well as others.
“It is our hope that our model [will enable] scientists to ask what might be an effective way of inducing interferons to block Zika virus spread within the individual and from mother to fetus,” she told Contagion. “We believe that our results will have an important impact on how future research effort on Zika virus will be shaped, for example through informing the direction with which to identify compounds that block vaginal replication of Zika virus, and by eliciting future studies of viral transmission from infected woman to uninfected man or woman.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.