Human cells can 'silence' HIV genes
For the first time, scientists have shown that humans use an immune defense process common in plants and invertebrates to battle a virus. The new finding that human cells can silence an essential part of HIV's genetic make-up could have important implications for the treatment of people infected with the virus. Led by Kuan-Teh Jeang, M.D, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID), part the National Institutes of Health, the researchers published their findings in this week's issue of the journal Immunity.
"This research suggests that a novel approach to HIV therapy targeting a stable component of HIV might be feasible," says NIAID Director Anthony S. Fauci, M.D.
The phenomenon, called RNA silencing, was detected first in plants and later in insects. Although plants and insects lack the sophisticated immune defenses of higher organisms, they nevertheless successfully battle viruses by detecting, and then silencing, viral genetic material. Silencing leads to the destruction of viral RNA. Viruses, however, are not permanently defeated because they have evolved ways to suppress the silencing action.
The most unexpected finding, according to Dr. Jeang, was the way HIV uses one of its proteins, called Tat, to suppress the silencing efforts of the cell. HIV is well known for evading drugs by quickly mutating its genes. However, the virus could not evade the newly discovered sequence-specific siRNA attack by mutation. Instead, HIV required a virally encoded protein to blunt the assault. Dr. Jeang believes that Tat may be shielding a rare HIV Achilles' heel, a genetic sequence that, for functional reasons, the virus cannot change in order to escape siRNA attack. This novel siRNA sequence discovered by the team may lead to the development of new RNAi-based drugs to which HIV would not be able to develop resistance by simple mutation.
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