Herpes Virus Mimics Host Defense Proteins

A study has found that complement plays a key role in host defense against gamma-herpes virus (gHV) infection, and that gamma-herpes viruses have evolved an immune evasion strategy that is effective against complement-mediated antiviral responses during acute but not latent infection. The study was published in the August 2002 issue of Immunology.

Healthy cells produce molecules known as regulators of complement activation (RCA) to prevent inadvertent triggering of the complement system. In the current study, researchers from Washington University School of Medicine (St. Louis, MO, USA; www.wustl.edu) used a genetically engineered strain of mouse gamma-herpes virus 68 (gHV68) which lacked a protein that mimics mouse RCA protein. They compared the effects of the normal RCA-containing virus and the mutant virus on normal mice versus mice that lacked a key complement protein, C3.

The virus strain lacking the RCA mimic protein was far less virulent than the normal virus. About 100 times more of the mutant virus was required to infect healthy mice than was the normal virus. The mutant virus grew 27 times slower than the normal strain and failed to spread to other organs during acute infection. When the genetically engineered virus was injected into mice lacking C3, it was just as virulent as the normal viruses are in normal mice, since the virus did not need to disguise itself with RCA in order to thrive.

The researchers found that while healthy mice infected with gHV68 rarely showed signs of persistent infection, this condition readily occurred in C3-deficient mice. Furthermore, during latent infections three to five times more virus could be reactivated in C3-deficient mice than in normal mice.

"These findings reveal another molecular mechanism by which viruses evade the immune system,” said study leader Dr. Herbert W. Virgin, professor of pathology and immunology and molecular microbiology at Washington University. "Our findings explicitly show that complement plays a role during persistent and latent infection, and that was unexpected. They also emphasize that we cannot study a viral protein during just one part of a virus's life cycle and assume we understand the function of that protein. It is important to look at it during all phases of infection.”



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