Virus Hijacks Cell Division Machinery

Cytomegalovirus in a specimen of embryonic lung tissue

Widespread virus with potential
to disrupt cell control; © PHIL

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 University of Wisconsin-Madison Institute for Molecular Virology, who led the study. "This pathway is mutated in essentially all human cancers."

Disrupting this pathway is also advantageous for viruses. Viruses rely on co-opting their host's cellular machinery. They are especially good at overriding or bypassing built-in control mechanisms, Kalejta says. The researchers now report that a viral protein, called UL97, masquerades as a normal regulatory enzyme to modify a tumor-suppressing protein in human cells.

"Viruses are well known to encode proteins that have similar activities to cellular proteins," he says. "[UL97] shares the same activities as the cellular protein, but it lacks all of the control mechanisms." In essence, UL97 disables the brakes and hits the gas. Once a host cell is primed toward growth, HCMV takes over and steals the cell's machinery to reproduce itself.

The virus's bloodhound-like ability to seek out and target the most essential pieces of a cell's machinery makes it a valuable research tool, Kalejta says. "Viruses are smarter than we are. They know a lot more about cells than we do, because their life depends on it“, he says. "If they attack a part of the cell - a process or a protein - you know it's important for the cell. If the virus pays attention to it, you should too."

Kalejta next hopes to use UL97 to find other proteins that may be important for cell growth. He also sees potential clinical applications down the road. HCMV infection is very common and, though it remains asymptomatic in most people, it has been implicated in some cancers and can cause trouble in people with compromised or suppressed immune systems, such as AIDS patients and transplant recipients.

MEDICA.de; Source: University of Wisconsin-Madison