Tunnelbuilding virus: How Zika takes over from mother to fetus

Zika is an orthofloflavivirus member of the Flaviviridae family, which also includes viruses from westnile, dengue and yellow fever. In this case, mosquitoes are the vectors. In contrast to other flaviviruses, Zika can also be transferred between people in the absence of a vector and is the only flavivirus to cross the placenta lock from an infected mother to a fetus.

Zika infections among adults are usually not serious, the researchers explained. However, if a pregnant woman is infected, there is a possibility that the virus can affect the development of the fetus, which leads to neurological disorders and other anomalies. There is currently no vaccine or antiviral medication for Zika.

“It is important to prevent this infection from going to a fetus,” said Joyce Jose, Associate Professor of Biochemistry and Molecular Biology at Penn State and co-author of the study. While human infections of the Zika virus have decreased, Jose said the danger of future epidemic residues, especially since mosquitoes could spread to new and various regions due to changes in climate and weather that could spread to new and different regions.

It was a coincidence that the team of Zika's ability discovered to build tiny tunnels. Researchers investigated living in the Penn State, which were infected with the Zika virus under a fluorescent microscope, when they noticed long tube-like structures, the neighboring cells, plasma membrane with plasma membrane. When they looked at other viruses infected cells such as dengue and yellow fever, they saw no tubes. In the meantime, Baylor researchers also found that Zika induced the formation of nanor tubes in placenta cells. When the two groups shared their results, they carried out more tests and found that the tiny tunnels in placental were actually more pronounced.

Viruses such as HIV, Herpes and Sars-Cov-2-Das Virus, the Covid-19 building also causes tiny tunnels and spread them on non-infected cells, but these viruses do not cross the placenta. In experiments in human placenta cells in vitro, which means in a cultural bowl, the team found that Zika produces tunnels infected with Zika for non -infected cells. The cells were procured by a cell line available in stores.

The cell-to-cell compounds act as lines and enable virus particles, proteins and RNA to be transported by infected cells to adjacent cells.

“If there is a virus outside the cell, it can be caught by antibodies in the bloodstream. But the tubes act like an extension of the cell, so that the virus is protected by antibodies and not neutralized, ”said Jose. In other words, the immune system hides the virus. When the Placenta cells team examined, which were infected with the Zika virus and could not construct nanor tubes, the growth and spread of the virus was reduced.

But material not only flows through the tiny tunnels in one direction. Mitochondria, the main energy source of the cell, are harvested from the non -infected cell and sibloned by these tubes into the infected cell.

“It's a two-way street,” said Narayanan. “The virus reprograms the entire cell to improve its growth. It collects mitochondria so that it has energy, survive and spread out on non -infected cells around them. “

The team also discovered that the protein NS1 is responsible for the development of tiny tunnels. NS1 is an important protein for flavivirus and plays an important role in viral replication, but it does not spur the development of nanor tubes in the other viruses. The researchers identified the specific area of ​​the Zika NS1, which was involved in the construction of the tubes. Shay Toner, co-author of the study and doctoral student at the Massachusetts Institute of Technology, identified the region as part of his thesis in the Bachelor-Ehrenthese in Penn State. According to Joyce, his research was an essential part of the role of NS1 in the formation of Nanotubes.

“I was interested in the Zika outbreak in 2015 as a high school for virology,” said Toner. “It was an astonishing opportunity to work on Zika in Jose Lab from Penn State and play a small role in such a effective project.”

Next, the team will work on identifying the specific signal path activated by NS1, which leads to the creation of the tunnels. In this way, they hope to identify potential drug goals for antiviral drugs. You will also start studies in a mouse model.

“It's like a detective story. We do not yet understand the mechanism of how these tubes are formed, so we continue to ask further questions, ”said Jose.

The authors of the newspaper of the Baylor College of Medicine include Indira Mysorekar, Ei Wagner duration, MD, Chairman of Internal Medicine II and Professor of Medicine; Rafael Michita, postdoctoral research assistant; Long tran, doctoral student; Steven Bark, bioinformatics analyst; and Deepak Kumar, postdoctoral.

This work was partially supported by grants from the NIH National Institute of Allergy and Infectious Diseases (R01AI176505), the NIH National Institute of Child Health and Human Development (R01HD091218) and Penn State.