Viruses are little packets of destruction and there are more of them than any other biological entity on the planet.
Fortunately, only a few hundred are known to make people sick, and figuring out what causes those viruses can help prevent illness. In addition, examining how viruses have evolved to infect mammals may even answer fundamental questions about human health.
A study by a team at the University of Michigan Medical School takes a closer look at a virus that causes tumors in monkeys called SV40. SV40 is a DNA virus that settles in a cell and then in its nucleus, thereby infecting it to make more of itself.
“SV40 is being used as a tool to understand how viruses that cause cancer work in humans,” said Chelsey Spriggs, Ph.D., assistant professor, Cell & Developmental Biology and Microbiology & Immunology at UM Medical School, Research Assistant Professor at the UM Life Sciences Institute, and lead author of the study. Several viruses have been linked to cancer in humans, including human papilloma virus, Kaposi’s sarcoma-associated herpes virus, and Epstein-Barr virus.
The research team wanted to better understand how this infection process takes place in the cell. A previous study by Spriggs (at the time a postdoctoral researcher in the lab of Billy Tsai, Ph.D., the Corydon Ford Collegiate Professor of Cell & Developmental Biology), and their team, found that SV40 travels from the surface of the cell, through the endosome, the endoplasmic reticulum and then to the cytosol, where it is partially disassembled. The latest study highlights the final and most important step for infection, access to the nucleus.
The virus itself is larger than the portal it uses to access the cell nucleus, Spriggs explains, called the nuclear pore complex. The nuclear pore complex is an important gate in the membrane of the nucleus and regulates the transport of proteins, RNA and other cellular cargo from the nucleus to the cytoplasm of the cell and back again. Many viruses use this passage to sneak into the core.
Now published in PLOS pathogens, the new study found that SV40 uses the nuclear pore complex and another protein complex called LINC, which connects the inner and outer membranes of the nucleus, first tearing itself apart into a smaller package made up of two proteins and the virus’s genome. Unlike many other viruses that latch onto finger-like projections protruding from the nuclear pore complex, SV40 interacts with LINC first before entering.
This difference in technique could underlie SV40’s ability to cause cancer, Spriggs notes. Further investigation into how SV40 exploits LINC and the nuclear pore complex could even help scientists understand how the two major cellular membrane complexes interact, which is somewhat of a mystery until now.
“Viruses use many of the same pathways disrupted in cancers and other diseases,” Spriggs said. “Studying them is good for understanding human biology.”
Spriggs recently opened her own independent research lab at the University of Michigan, where she studied the entry mechanism of human oncogenic viruses.
Other authors of this article are Grace Cha and Jiaqian Li.
Study identifies different roles for nuclear lamin . isoforms
Chelsey C. Spriggs et al, Components of the LINC and NPC complexes coordinately target a virus and move it to the nucleus to promote infection, PLOS pathogens (2022). DOI: 10.1371/journal.ppat.1010824
Quote: The unique way this virus sneaks into the cell nucleus could advance the study of cancer-causing pathogens (2022, October 18) retrieved October 18, 2022 from https://phys.org/news/2022-10-unique-virus-cell -nucleus-advance.html
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