Stanford scientists help bring study of smallpox virus into 'molecular age'

urviving samples of virus to learn more about the disease.

Relman, along with biochemistry professor Patrick Brown, MD, PhD, and graduate student Kate Rubins, looked for the genes that were activated or repressed in the circulating blood cells of monkeys infected with smallpox. They identified these genes by comparing blood samples obtained repeatedly during the course of infection with those obtained from the same monkeys prior to infection. Their goal was to understand better the strategy used by smallpox virus, as well as the defense strategy of the primate host. Additionally, they compared smallpox infection with Ebola infection to tease apart the changes that might be relatively specific to smallpox rather than those that generally occur in overwhelming viral infections.

To see which genes were activated during infection and which ones were repressed, the team used DNA microarrays - glass slides containing pieces of DNA corresponding to each of approximately 18,000 different genes. They found several key components of the immune system that appeared to respond differently to smallpox than to Ebola.

One of the most intriguing aspects of their results, said Rubins, the first author of the paper analyzing the host response to smallpox, was the glimpse they provide of the highly orchestrated interaction between the infected host animal's immune system and the virus. Most striking, she said, was that certain critical molecules that control immune response were shut down in smallpox infection but not Ebola, indicating that smallpox may be producing inhibitors of these molecules.

Of particular interest in future studies, said Relman, is to identify the events that happen soon after infection - the "early molecular signatures" associated with the virus. Such markers could be useful in guiding interventions in the event of a smallpox outbreak.

Smallpox transmits only among humans. Since the d

Contact: Mitzi Baker
Stanford University Medical Center

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