Have Researchers Discovered Another Pathway for Zika Virus Transmission?

A multidisciplinary team of researchers from Washington University in St. Louis, Missouri and Colorado State University in Fort Collins, Colorado, may have identified another potential pathway for transmission of Zika virus: tears.

Following up on earlier studies that have revealed links between the mosquito-borne virus and ocular diseases such as conjunctivitis and uveitis as well as ocular defects in newborns, the authors of a paper published online on September 7 by the journal Cell Reports used recently developed mouse models to assess the effects of Zika on the eye. They found that the Zika-inoculated mice in their experiment developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. They also noted that Zika RNA can be detected in tear fluid.

“Although cases of eye involvement with congenital and adult infection have been reported [with Zika], the molecular pathogenesis was unclear,” said study co-author Rajendra S. Apte, MD, PhD, Paul A. Cibis Distinguished Professor of Ophthalmology and Developmental Biology and Medicine at Washington University School of Medicine. “It was also unclear if virus directly involved the eye. We wanted to examine this and model it.”

According to Dr. Apte’s colleague and co-author, Michael Diamond, MD, PhD, Herbert S. Gasser Professor of Medicine, Molecular Microbiology, Pathology and Immunology at Washington University, as many as 15% of adults with Zika develop conjunctivitis, or redness in the eyes. However, theirs is the first study to suggest that the eyes may serve as a “reservoir” for the virus, although it remains unclear how its cells travel there, whether they cross the blood-retina barrier or take some other pathway. They also are the first to confirm that Zika RNA is present in tears up to 28 days following initial infection, making it possible that the virus could be transmitted through contact with the tears of those infected. Although their tests found the presence of viral RNA in tears, they also revealed that live virus was not present in the fluid.

“There are implications for transmission although analogous findings have to be demonstrated first in human tears,” Dr. Diamond noted.

Both authors also suggested that their findings may have implications for Zika diagnosis and treatment. Dr. Diamond, for example, said that human tear fluid could possibly serve as a reliable diagnostic source, particularly “if virus or viral RNA can be detected persistently”—an issue that has plagued blood and urine sample testing to date. He added that the eye is also “a good place to attempt local treatment and to evaluate efficacy [of] candidate antivirals [once they] are identified.”

“The eye is an immune privileged organ,” Dr. Apte said. “Several systemic agents have been repurposed for eye disease by targeting the eye with local delivery. This often avoids larger doses required for systemic treatment and off-target toxicity as smaller disease can be delivered directly to the eye. So, the eye is an excellent testing ground for drug development against Zika or other viruses that are playing havoc.”

Of course, the findings of the Cell Report study first need to be replicated in humans before any firm conclusions can be drawn. Drs. Apte and Diamond told Contagion that their lab is already working on human studies and they are in the process of developing a “diagnostic protocol using tear sampling.”

Dr. Apte added, “We would also like to perform additional mouse studies to demonstrate which receptor is or receptors are involved in viral entry into the eye and whether the virus comes to the eye from the blood stream or from the central nervous system. These would just be the beginning of understanding pathogenesis [of Zika] and moving towards theranostics and therapy [for the virus].”

In addition, Dr. Apte and his team are interested in studying the implications for corneal transplants in edemic areas. He stated, "Given that we discovered that there was evidence of viral particles in the corneal stroma, it would be important to investigate the implications for corneal transplantation in endemic areas. Corneal transplantation is the most common and most successful transplantation in humans. Using animal models, we would like to examine whether our findings have clinical/translational implications for corneal transplantation."

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.