Researchers at Baylor College of Medicine, in collaboration with Pennsylvania State University, have uncovered a mechanism by which the Zika virus spreads through placental cells. Their findings, published in Nature Communications, reveal that the virus uses tunneling nanotubes to move between cells without triggering significant immune responses.
"The Zika virus, which is transmitted by mosquitoes, triggered an epidemic in the Americas that began in 2015 and by 2018 had reached as many as 30 million cases," stated Dr. Indira Mysorekar from Baylor College of Medicine. Understanding the transmission method is crucial for developing preventive measures against this condition.
The study highlights that these tiny tunnels are formed due to a Zika protein called NS1. "Exposure of placental cells to the NS1 protein of Zika virus triggers tunnel formation," explained Dr. Rafael T. Michita from the Mysorekar lab. These tunnels allow not only viral particles but also RNA, proteins, and mitochondria to transfer between cells.
Dr. Michita noted that while other viruses like HIV and SARS-CoV-2 can also form similar structures, Zika's use of tunnels in placental cells is unique within its viral family. The transport of mitochondria through these conduits may boost energy levels in infected cells, aiding viral replication.
"We propose that transporting mitochondria through the tunnels may provide an energetic boost to virus-infected cells," added Long B. Tran from the research team.
Moreover, this mode of transmission helps Zika evade antiviral responses such as interferon lambda defenses typically activated by the placenta. "Mutant Zika viruses that do not make tiny tunnels induce robust antiviral IFN-lambda response," Michita said.
Dr. Mysorekar concluded that their findings offer insights into potential therapeutic strategies targeting this covert transmission method: "We propose that this strategy also protects the virus from the immune response."
The research involved key contributions from Steven J. Bark and Deepak Kumar at Baylor College of Medicine and Shay A. Toner, Joyce Jose, and Anoop Narayanan at Pennsylvania State University.
Funding for this study was provided by grants from NIH/NIAID (R01AI176505), NIH/NICHD (R01HD091218), Pennsylvania State University startup funds, CPRIT Core Facility Support Award CPRIT-RP180672, and NIH (CA125123 and RR024574).
