How a sneaky virus drives cancer cells to grow

As scientists identify ways that viruses exploit their host cells to make more copies of themselves, they are also uncovering clues to how these viral invaders trigger cancerous cell growth.

A new study shows how a type of herpesvirus uses mimicry to trick the host cell into producing proteins the virus needs, and to drive cell growth. The findings have implications for how the virus causes cancer, researchers say.

The Kaposi sarcoma-associated herpesvirus makes a protein called vPK that shares a number of similarities to a host cell protein named S6KB1. The virus manipulates the S6KB1 host cell signaling pathway to spur the host cell to make more proteins and divide—even when the host isn’t ready for it. The findings shed light on a potential cancer-causing mechanism of the virus.

How cells know when to stop growing and split

“Cancer is a multi-step process, and to turn a normal cell into a cancer cell, a number of events need to occur,” says senior author Blossom Damania, professor of microbiology and immunology at the University of North Carolina at Chapel Hill.

“Some of those steps involve increasing cell proliferation, others involve preventing cell death, and yet others involve the cell evading host immunity.

This process usually requires multiple events that target these different pathways before a cell becomes cancerous. We think that different viral proteins are targeting different cell pathways, and the one we identified in this study is targeting cell protein synthesis and cell growth.”

Kaposi sarcoma-associated herpesvirus is linked to several types of cancer, including Kaposi sarcoma and two types of lymphomas. People who have a weakened immune system, such as transplant recipients who take immune suppressive drugs or those infected with HIV, are at increased risk of developing Kaposi sarcoma when infected with the virus.

Checks and balances

Previous studies have shown that Kaposi sarcoma-associated herpesvirus can make proteins that keep the host cells from triggering its own death, or that prevent warning signals to the body’s defense system in response to the virus.

In the new study, published in the Proceedings of the National Academy of Sciences, researchers used computer modeling to reveal that the viral protein vPK is structurally similar to a host protein. They also used other biochemical and molecular methods to determine that the two proteins target similar signals in the cell.

Based on those and other findings, they conclude that the viral protein mimics the human protein’s function, causing the host cell to increase protein production, to divide, and to encourage angiogenesis, a process by which tumors induce blood vessels to fuel them with nutrients.

With such virally-promoted functions relatively unchecked, those functions can contribute to the abnormal cell growth that’s characteristic of cancer.

Cancer cells escape when they block this gene

“This viral protein does not contain the same ‘checks’ that keep the cellular protein in line, so it can perform this function without being controlled by the brakes the cell normally uses to control activity of the cellular protein,” Damania says. “So essentially, the viral protein can function unregulated, and hence, might contribute to the development of cancers associated with this virus by augmenting cell proliferation.”

The findings may also have implications for treatment of viral cancers, says first author Aadra Bhatt, a postdoctoral researcher at UNC Lineberger.

And although the new findings uncovered the similarity between the viral and host protein, researchers speculate that the virus has been evolving alongside humans and their evolutionary ancestors for millions of years to enable them to commandeer host cell pathways and use the host to their own advantage.

The National Institutes of Health, the American Cancer Society, the Leukemia and Lymphoma Society, and the Burroughs Wellcome Fund supported the work.

Source: UNC-Chapel Hill

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Source: Futurity