Researchers at the University of Arizona awarded a $1.8 million grant to study HPV cellular invasion

Researchers at the University of Arizona awarded a $1.8 million grant to study HPV cellular invasion

Researchers at the University of Arizona College of Medicine – Tucson received a $1.8 million grant from the National Institute of General Medical Sciences, a division of the National Institutes of Health, to find out how the human papillomavirus enters the cell nucleus.

The human papillomavirus, or HPV, which can cause warts and certain cancers, has been with us since the dawn of humanity and causes about 5% of all cancers worldwide. It is also an important source of information about human biology, according to Samuel K. Campos, PhD, associate professor of immunobiology at the University of Arizona College of Medicine – Tucson and member of the BIO5 Institute.

"These viruses exploit and optimize the cell's signaling pathways. What better cell biologists could teach us how cells work than the viruses that have evolved with us for eons?" Campos said about how HPV illuminates the inner workings of our bodies. “Follow the biology of the virus and we’ll learn some cool new cell biology.”

Campos said there are more than 600 known strains of the human papillomavirus, with more yet to be discovered. His lab focuses primarily on HPV16, the type that causes most cervical, anal and head and neck cancers.

HPV has found its niche in certain types of epithelial cells that cover our bodies as skin and line our body cavities as mucous membranes. The virus travels from the lower layers of the epithelium to the upper layers, and once it approaches the surface, replication goes into overdrive as it prepares to leave one body and infect another.

We are constantly losing dead skin -; it simply detaches from our body. This is how HPVs have spread so successfully through the human population.”

Samuel K. Campos, PhD, associate professor of immunobiology at the University of Arizona College of Medicine – Tucson

HPV genes are packaged in a protein coat. The Campos lab is focusing on the role of one of these coat proteins, L2, which can insert and enter the membranes of our cells like a key in a lock. Upon entry, the virus is guided along a convoluted path to the cell nucleus, where it hijacks the cell to make copies of itself.

Campos said his lab's previous research has shown that from the cell's perspective, L2 looks like a different part of the cell.

“We learned that the virus is really insidious,” Campos said. "L2 can actually penetrate the cell membrane without destroying it, and HPV remains hidden behind these membranes. It can evade sensors that detect danger signals, like a wolf in sheep's clothing."

Previous research published by the Campos Lab and other groups suggests that HPV may be able to hide until the cellular machinery whirs into action during cell division. Then it sheds its “sheep’s clothing” and makes its way to the cell nucleus.

“Once the virus has successfully delivered its DNA genome into the cell nucleus, it can begin expressing its own genes to take over the cell,” Campos said. "This leads to evasion of the immune system, alteration of the cell cycle, formation of new virus particles and transmission to another host. If the virus remains long enough, these infections can sometimes alter the cell in ways that lead to cancer."

The five-year R35 fellowship that Campos receives is reserved for scientists with outstanding research results and the potential to make important contributions to their field. It gives researchers the flexibility to pursue their research in the direction they want. The grant will help the Campos lab learn how HPV exploits cell division to move from its hiding place in the cell to the cell nucleus.

"It's a complete black box. It would be really cool to figure that out," Campos said, adding that tracking the virus's path will shed light on the intricacies of cell division and how things move in and out of cells.

These unknowns are what keep Campos coming to work every day.

"It's hard and frustrating, but it's also satisfying - like solving a puzzle," he said. "You don't know where science will take you. You don't know what the end will be. That's exciting."

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