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Cause of hepatitis A virulence pinpointed

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have located two genes that give hepatitis A virus (HAV) its virulent properties. The team, led by Suzanne Emerson, Ph.D., also has discovered that deliberately weakened HAV can quickly revert to its naturally occurring, infection-causing form. To be published in the September 1 issue of Journal of Virology, and appearing online this week, these findings indicate that making an improved vaccine for HAV will be a very difficult task.

"As sanitation improves in developing countries, there will be an increased need for inexpensive and easy-to-administer vaccines to prevent hepatitis A, which is transmitted through contaminated food and water," notes Dr. Emerson. HAV is so common in developing countries that almost everyone is infected during childhood (often without becoming noticeably ill) and thereafter is immune to the virus. Improvements in sanitation and water quality, though, make such naturally acquired immunity less likely. Unfortunately, if HAV infection occurs for the first time later in life, it can result in dangerous illness, including severe liver damage.

A vaccine made from killed HAV does exist, but it requires multiple booster shots to be given intramuscularly-an expense and inconvenience that inhibits its use in less developed countries. Scientists at NIAID have been attempting to develop a live, attenuated HAV vaccine. An attenuated vaccine-one made from a deliberately weakened form of the virus-could be given orally in a single dose, a clear advantage to the existing vaccine.

To develop such a vaccine, Dr. Emerson and her coworkers first had to determine which genes give HAV its punch. They compared the genetic make-up of a virulent version of human HAV with that of an attenuated version of the same strain of virus by creating 14 artificial "chimeric" viruses, each of which contained a different combination of genes taken from the par
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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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