The unique way this virus sneaks into the nucleus could facilitate research into carcinogenic pathogens

Viruses are tiny packets of destruction, and there are more of them than any other biological entity on Earth
.

Fortunately, only a few hundred viruses are known to make people sick, and figuring out what causes them can help prevent disease
.
What's more, studying how viral infections have evolved in mammals can even answer fundamental questions
about human health.

A team of researchers at the University of Michigan School of Medicine took a closer look at SV40
, a virus that causes tumors in monkeys.
SV40 is a DNA virus that, in order to make more of itself, burrows into cells and then into the nucleus, infecting cells
.

"SV40 is used as a tool for work to understand how viruses cause cancer in humans," said Dr.
Chelsea Spriggs, an assistant professor of cell and developmental biology, microbiology and immunology at the University of Michigan School of Medicine and a research assistant professor at the University of Michigan's Life Sciences Institute and first author
of the study.
Several viruses have been linked to human cancer, including human papillomavirus, Kaposisarcoma-associated herpesvirus, and Epstein-Barr virus
.

The team hopes to gain a fuller understanding of how this infection process occurs
inside cells.
An early study by Spriggs (who was then a postdoc in the lab of Dr.
Billy Tsai, a professor of cell and developmental biology at Fridenford College) and their team found that SV40 travels from the cell surface, through endosomes, endoplasmic reticulum, and then reaches the cytoplasm, where it is partially broken down
.
The latest research sheds light on the final and most important step of infection, which is entry into the nucleus
.

Spriggs explained that the virus itself is larger than the entrance it uses to enter the nucleus, which is called the nuclear pore complex
.
The nuclear pore complex is a major port on the cell membrane of the nucleus, regulating the transport
of proteins, RNA, and other cellular cargo from the nucleus into the cytoplasm and back.
Many viruses use this pathway to sneak into the nucleus
.

The new study found that SV40 uses the nuclear pore complex and another protein complex called LINC (LINC connects the inner and outer membranes of the cell nucleus) to first break itself down into a smaller package
made up of two proteins and viral genomes.
Unlike many other viruses that grasp the finger-like protrusions of the nuclear pore complex, SV40 interacts
with the LINC before entering the LINC.

Spriggs noted that this technical difference could underlie
SV40's carcinogenic ability.
Further research into how SV40 utilizes LINC and the nuclear pore complex could even help scientists understand how these two important cell membrane complexes interact, which has so far been a mystery
.

"The virus uses a lot of the same pathways that are destroyed in cancer and other diseases," Spriggs said
.
"Studying them helps to understand human biology
.
"

Spriggs recently opened his own independent research lab at the University of Michigan to study the entry mechanism
of human oncogens.