Virus mimics human protein to hijack cell division machinery

MADISON - Viruses are masters of deception, duping their host's cells into helping them grow and spread. A new study has found that human cytomegalovirus (HCMV) can mimic a common regulatory protein to hijack normal cell growth machinery, disrupting a cell's primary anti-cancer mechanism.

Writing in the May 9 issue of Science, researchers from the University of Wisconsin-Madison and Harvard Medical School report that a viral protein, called UL97, masquerades as a normal regulatory enzyme to modify a tumor-suppressing protein in human cells. Unlike the normal enzyme, which can be switched on and off by the cell as needed, the viral stand-in lacks an off switch and evades cellular control. The findings represent a previously unknown way that viruses can cause uncontrolled cell growth and division.

Cells normally have tight regulatory mechanisms in place to limit multiplication to appropriate situations, such as replacing worn-out cells or repairing damage. Uncontrolled cell proliferation can lead to cancer and other disorders.

One of the most important cellular control mechanisms works through a protein called the retinoblastoma tumor suppressor protein, which slows cell growth.

"The retinoblastoma pathway is like the brakes on a car. It prevents tumor cells from growing out of control," says Robert Kalejta, an assistant professor in the UW-Madison Institute for Molecular Virology and McArdle Laboratory for Cancer Research, who led the new study. "This pathway is mutated in essentially all human cancers."

Disrupting this pathway is also advantageous for viruses. Unable to reproduce on their own, viruses rely on co-opting their host's cellular machinery, like an occupying army taking over a local factory. They are especially good at overriding or bypassing built-in control mechanisms, Kalejta says.

"Viruses are well known to encode proteins that have similar activities to cellular proteins, but they're just different enough that they're beneficial to the virus," he says. "[UL97] shares the same activities as the cellular protein, but it lacks all of the control mechanisms."