Researcher Uncovers Zika Virus Pathway to Placenta Using Nanotubes

A researcher at Baylor College of Medicine has made significant strides in understanding how the Zika virus infiltrates the placenta, a crucial barrier that typically protects the developing fetus. In March 2021, during his postdoctoral studies, Rafael Michita observed thin filaments connecting infected placenta cells to neighboring ones under a microscope. This observation led him to hypothesize that these connections, known as tunneling nanotubes (TNTs), could play a critical role in viral transmission.

Initially, Michita’s colleagues were uncertain about the relevance of these structures, but he felt compelled to investigate further. Having moved from Brazil, where he focused on genomic studies linked to pregnancy disorders, he was keen to apply his knowledge to this new area of research. His work has garnered attention, positioning him as a leader in the field of maternal-fetal viral transmission.

Tunneling nanotubes, which facilitate communication between cells by transferring molecules and organelles, have been previously associated with viruses like HIV, influenza A, and SARS-CoV-2. Michita’s findings suggest that Zika virus may exploit these nanotubes to breach the placenta and spread, a discovery that could lead to new therapeutic strategies aimed at preventing viral transmission.

Exploring the Role of Tunneling Nanotubes

The implications of Michita’s work extend beyond Zika. His research indicates that the virus not only uses TNTs for cell-to-cell spread but also siphons mitochondria from healthy cells into those infected, potentially enhancing viral replication. Olena Shtanko, an assistant professor at the Texas Biomedical Research Institute, noted that the role of mitochondria in this process is crucial. “TNTs are not going anywhere, and I think we’re going to see a lot more evidence that they contribute to viral pathogenesis,” she stated.

Tunneling nanotubes were first identified in human cells in the early 2000s as a means of direct cellular communication. Despite their potential significance, the application of this knowledge to viral research has been slow. Michita encountered the concept of TNTs primarily in the context of cancer, where they were shown to facilitate the transfer of mitochondria from healthy cells to tumors, thereby promoting cancer growth.

Indira Mysorekar, a professor at Baylor College of Medicine and Michita’s mentor, praises his ability to connect diverse scientific concepts. “I knew right away he was onto something exciting,” she remarked, emphasizing his holistic approach to research. Michita’s background in genetics and his fascination with biological processes have enabled him to explore innovative avenues of inquiry.

A Multicultural Journey to Scientific Discovery

Michita credits his multicultural upbringing in Brazil for nurturing his inquisitive nature. With grandparents who immigrated from Japan, he developed a love for exploration and learning. Growing up in the countryside, he found solace in nature and books, fostering a lifelong interest in biology. He began university at the young age of 16 and pursued further studies abroad, including time spent in New Zealand and Germany, where he gained specialized training in immunogenetics.

The Zika virus epidemic in Brazil from 2015 to 2016 sparked a shift in Michita’s research focus. Witnessing the urgent need to understand how the virus transmitted from mother to fetus, he recognized the necessity of expanding his skill set beyond genetics. “The lack of understanding of how the virus infects the placenta… made it clear that I needed to expand my skill set,” he explained.

At Baylor, Michita joined a leading laboratory dedicated to Zika virus research. Scientists there analyze placental samples from infected mothers and test experimental treatments in mouse models while tracking the molecular dynamics of infection using advanced cell culture techniques. Mysorekar encourages scientists to think creatively and integrate their ideas into the broader framework of the laboratory, fostering an environment of innovation.

In the coming two years, Michita plans to establish his own laboratory, supported by the NIH Pathway to Independence Award. His research will broaden to include HIV, exploring how this virus also utilizes TNTs for transmission to placental cells. Early experiments have suggested that HIV-infected immune cells may employ similar mechanisms.

As Michita prepares to advance his research, he reflects on his groundbreaking work with the Zika virus. By focusing on the NS1 protein, crucial for TNT formation, he has made strides in understanding how to disrupt viral transmission. Preliminary findings indicate that disabling NS1 in pregnant mice could protect their offspring from birth defects.

“This is just the beginning,” Michita stated, emphasizing the potential for further exploration in the field of virology and tunneling nanotubes. His journey underscores the importance of curiosity and interdisciplinary approaches in addressing complex biological questions. As he continues to unravel the mysteries of viral transmission, Michita is poised to make significant contributions to maternal-fetal health and disease prevention.