The researchers found that viruses lacking an RCA mimic were far less virulent than the normal virus: It took 100 times more of the mutant virus to cause disease in healthy mice compared to normal virus. The mutant virus also grew 27 times slower than normal, and it failed to spread to other organs during acute infection. This showed that the RCA mimic proteins were necessary for the virus to thrive.
Next, the researchers tested the mutant virus in mice lacking C3. In this case, the mutant virus was just as virulent as normal viruses in normal mice. Without C3 in the infected animal, the virus did not need to disguise itself with RCA in order to thrive. This implies that, in normal mice, the mimic protein enabled the virus to escape detection by the complement system.
The investigators then explored the role of complement and RCA during persistent and chronic infections. Historically, scientists believed that the body uses the complement system only during the initial, or acute, phase of herpes virus infection. Chronic stages of infection, they thought, were fought by immune system components such as T cells, B cells and interferons.
Persistent infection occurs when the virus continues to replicate beyond the period of acute infection. It is most clearly seen when the immune system is seriously impaired. Latent infection occurs when the virus resides inactively in cells, but it can be reactivated to generate infectious virus.
The researchers found that while healthy mice infected with gHV68 rarely showed signs of persistent infection, this condition readily occurred in C3-deficient mice. This was evidence that complement helped control this phase of infection.
They also discovered that complemen
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Contact: Darrell E. Ward
wardd@msnotes.wustl.edu
314-286-0122
Washington University School of Medicine
20-Aug-2002