A graduate student at the Whitehead Institute for BiomedicalResearch and her lab director have discovered a way that fluviruses spring into cells. The same mechinism may be involvedin the AIDS virus, and could also occur in healthy kinds ofmembrane fusion, such as nerve firing.
Research on this new target for anti-viral drugs byMassachusetts Institute of Technology (MIT) student ChavelaCarr and professor Peter Kim is being published in today's issueof the journal Cell.
Scientists know that as infection starts, viruses are enfoldedinto bubbles of the cell membrane called endosomes. The viruscannot commandeer the cell and multiply until its ownmembrane fuses with the endosome and the viral geneticmaterial pours out into the cell.
The part of the virus responsible for this function, however,seemed to be too deep within the virus coat to work. In fact,trying to understand fusion was like trying to imagine pluggingin a floor lamp with a one-foot cord when the outlet was in theceiling.
The two scientists discovered that this "cord" was, in fact, astructure called a coiled coil, a sort of molecular ringletnormally bent like a hairpin that, in the acidic fluids of theendosome, uncoils like a harpoon and makes the membranesfuse.
The spring has two pieces of protein, which Carr compares to aspring and clamp.
The HIV coat protein also has two pieces, one with strikingsimilarities to the spring-like region of the so-calledhemagglutinin protein, which the team analyzed from the fluvirus.
The researchers have also looked at known structures in sixspecies as diverse as yeast and humans, and found a familiarmolecular pattern in the spring of a common protein,synaptobrevin, that allows nerve synapses to relayneurotransmitters and has other functions in the simplerorganisms.
"We believe that many different viruses may use the spring-loaded mechanism to initiate fusion," Carr said. "We're justbeginning to assess how general the process really is."
Already, she said, a team led by T. Matthews at DukeUniversity has reported a possible therapeutic approach basedon this process. In 1992, Matthews and colleagues published apaper in the Proceedings of the National Academy of Sciencesshowing that a synthetic coiled-coil peptide from the spring-like portion of HIV, gp41, blocks the AIDS virus frommultiplying, perhaps by interfering with the spring-loadedmechanism.
-- Nancy Garcia Associate Editor
(c) 1997 American Health Consultants. All rights reserved.