Cause of hepatitis A virulence ...( ent strains. Monkeys exposed to a viru...)

ent strains. Monkeys exposed to a virus that contained either of two genes, 2C or VP1/2A, from the virulent parent developed symptoms of hepatitis. When both genes from the virulent parent were present, the disease was markedly more severe. Conversely, chimeras containing mutated forms of 2C and VP1/2A did not cause disease.

Weakening HAV by altering its two virulence-determining genes would seem to be a logical way to produce a hepatitis A vaccine. But when the researchers infected monkeys with just such an attenuated virus, it mutated within those animals, although it did not cause disease. Feces from the animals, however, contained infectious particles that could cause hepatitis in other monkeys.

"Although these results suggest that a live, attenuated HAV vaccine may be difficult to develop, they do help us better understand what controls HAV growth," notes Dr. Emerson. "Ultimately, this knowledge may provide us with a roadmap to a less expensive and more potent killed vaccine that could be used worldwide."

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Contact: Anne Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
8-Aug-2002

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