A number of ZIKV strains induce TNT formation in human placental trophoblast cells and switch viral proteins. Credit score: Nature Communications (2025). DOI: 10.1038/s41467-025-56927-2
An infection with Zika virus in being pregnant can result in neurological issues, fetal abnormalities and fetal dying. Till now, how the virus manages to cross the placenta, which nurtures the growing fetus and varieties a powerful barrier in opposition to microbes and chemical substances that would hurt the fetus, has not been clear. Researchers at Baylor Faculty of Medication with collaborators at Pennsylvania State College report in Nature Communications a method Zika virus makes use of to covertly unfold in placental cells, elevating little alarm within the immune system.
“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 co-senior creator Dr. Indira Mysorekar, E.I. Wagner Endowed, M.D., Chair Inner Medication II, chief of primary and translational analysis and professor of drugs—infectious ailments at Baylor. “Understanding how Zika virus spreads through the human placenta and reaches the fetus is critical to prevent or control this devastating condition.”
The researchers found that Zika virus builds underground tunnels, a collection of tiny tubes referred to as tunneling nanotubes, that facilitate the switch of viral particles to neighboring uninfected cells.
“We discovered that the formation of these tiny tunnels is driven exclusively by a Zika protein called NS1,” stated first creator Dr. Rafael T. Michita, postdoctoral analysis affiliate within the Mysorekar lab. “Exposure of placental cells to the NS1 protein of Zika virus triggers tunnel formation. As the tunnels develop and connect neighboring cells, a path opens for the virus to invade new cells.”
“Zika is the only virus in its family, which includes dengue and West Nile viruses among others, whose NS1 protein triggers the formation of tunnels in multiple cell types,” Michita stated.
“Other viruses unrelated to Zika, such as HIV, herpes, influenza A and SARS-CoV-2, the virus that causes COVID-19, can also induce tiny tunnels in cells they infect and use the tunnels to spread to uninfected cells. This is the first time that tunneling has been shown by Zika virus infection in placental cells.”
The N-terminus of ZIKV-NS1 is critical to induce TNT formation. Credit score: Nature Communications (2025). DOI: 10.1038/s41467-025-56927-2
Curiously, the tiny conduits supplied a method to move not solely viral particles, but additionally RNA, proteins and mitochondria, a cell’s foremost supply of vitality, from contaminated to neighboring cells. “We propose that transporting mitochondria through the tunnels may provide an energetic boost to virus-infected cells to promote viral replication,” stated co-author Lengthy B. Tran, a graduate scholar within the Mysorekar lab.
“We also show that traveling through the tiny tunnels can potentially help Zika virus avoid the activation of large-scale antiviral responses, such as interferon lambda (IFN-lambda) defenses implemented by the placenta,” Michita stated. “Mutant Zika viruses that do not make tiny tunnels induce robust antiviral IFN-lambda response that can potentially limit the spread of the virus.”
“Altogether, we show that Zika virus uses a tunneling strategy to covertly spread the infection in the placenta while hijacking mitochondria to augment its propagation and survival. We propose that this strategy also protects the virus from the immune response,” Mysorekar stated. “These findings offer vital insights that could be used to develop therapeutic strategies targeted against this stealth transmission mode.”
Steven J. Bark and Deepak Kumar at Baylor Faculty of Medication and Shay A. Toner, Joyce Jose and co-senior creator Anoop Narayanan at Pennsylvania State College are key members of the analysis crew.
Extra data:
Rafael T. Michita et al, Zika virus NS1 drives tunneling nanotube formation for mitochondrial switch and stealth transmission in trophoblasts, Nature Communications (2025). DOI: 10.1038/s41467-025-56927-2
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Stealth virus: How Zika builds tunnels to covertly infect cells of the placenta (2025, February 21)
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