Innovative Research Uncovers Zika’s Path to the Placenta

Researcher Rafael Michita has made significant strides in understanding how the Zika virus infiltrates maternal tissues, particularly the placenta. His work at the Baylor College of Medicine in 2021 revealed the presence of thin filaments known as tunneling nanotubes (TNTs) connecting infected placental cells. This finding opens new avenues for understanding viral transmission between mother and fetus, potentially leading to innovative therapeutic strategies.

While observing the Zika virus under a microscope, Michita noticed these intercellular connections, which other lab members initially overlooked. “When I discussed this finding with my lab mates, they weren’t sure if these connections were worth studying further,” he explained. “But I thought, they cannot be nothing.” His determination to explore these structures reflects his background in genomic studies from Brazil, where he focused on genetic variations related to pregnancy disorders.

Understanding Tunneling Nanotubes

The role of tunneling nanotubes in viral transmission has gained traction in recent years. Michita’s research suggests that TNTs not only facilitate cell-to-cell spread of the Zika virus but also allow it to siphon mitochondria from healthy cells, potentially enhancing viral replication. This groundbreaking work indicates a critical pathway for viruses to breach the placenta, which acts as a protective barrier for the developing fetus.

Olena Shtanko, an assistant professor at the Texas Biomedical Research Institute, highlighted the novelty of Michita’s findings. “Tunneling nanotubes are a very out-of-the-box concept that, at first, wasn’t accepted by researchers. They needed more proof,” she noted. Her own research has shown that the Ebola virus also utilizes TNTs for its spread, underscoring the significance of these cellular structures in viral pathogenesis.

Despite initial skepticism, Michita’s findings align with earlier studies that identified TNTs as a means of communication in human cells, transferring nutrients and organelles over long distances. The application of this knowledge to viral infections represents a significant advancement in the field.

A Unique Perspective on Viral Infections

Indira Mysorekar, a professor at Baylor and Michita’s supervisor, praised his ability to integrate diverse fields of study. “He looks at everything holistically… and is able to integrate them in a very thoughtful, rigorous way,” she stated. Michita’s broad perspective stems from his multicultural upbringing in Brazil, where he developed a keen interest in biology and the complexities of pregnancy.

His experiences abroad, including time spent in New Zealand and Germany, further shaped his scientific outlook. “It’s important to move and get exposure to new things,” Michita emphasized. His fascination with pregnancy led him to explore how the immune system interacts with the fetus, an area of research crucial for understanding complications such as miscarriage and preeclampsia.

Michita’s shift towards studying cellular biology was catalyzed by the Zika virus epidemic in Brazil during 2015 and 2016. Observing the urgent need for answers regarding the virus’s transmission prompted him to broaden his expertise beyond genetic studies.

At Baylor, he joined a leading laboratory focused on Zika research. The team employs advanced techniques to analyze placental samples and investigate cellular responses to the virus. Michita’s contributions have been pivotal in revealing how Zika virus exploits the placenta, a finding that enhances the understanding of maternal-fetal health.

In the upcoming years, Michita plans to establish his own laboratory supported by the NIH Pathway to Independence Award. His research will expand beyond Zika to include other pathogens like HIV, which also utilizes TNTs for cellular invasion. Early experiments suggest that HIV-infected immune cells may similarly exploit these nanotubes to infect placental cells.

As Michita continues his research, he remains focused on the implications of his work. He aims to develop therapies targeting the vulnerabilities shared by viruses that utilize TNTs, with the hope of safeguarding maternal and fetal health. The role of the NS1 protein, essential for TNT formation, represents a promising area of exploration. Early findings indicate that disabling NS1 in pregnant mice could protect their offspring from birth defects, showcasing the potential for innovative treatments.

With an eye on the future, Michita’s work exemplifies the intersection of creativity and rigorous scientific inquiry. “We could see NS1 traveling through TNTs,” he recalled of a recent experiment. “The movement was so clear, how they were traveling from one cell to another.” His research underscores the growing importance of understanding viral mechanisms to inform clinical practices and improve health outcomes for mothers and their children.