Antiviral walls
http://www.100md.com
《细胞学杂志》
Defensins caught Chernomordik's eye because he works on membrane fusion and the defensins have broad specificity. He thought they might interfere with membrane properties, but was disappointed when they accelerated rather than inhibited fusion between protein-free liposomes.
With virus-infected cells, however, things got more interesting. Defensins did not block virus binding or endocytic uptake but did block membrane fusion. Membrane glycoproteins no longer diffused over the membrane surface.
The lack of diffusion may be the key. When a virus binds to a cell there is still a gap of 10 nm between the membranes, which can be closed only when proteins in a tiny patch happen, via random diffusion, to get out of the way. With defensins bound, suggests Chernomordik, "the proteins would not move away."
"This might be the first natural antiviral agent targeting fusion," says Chernomordik. "The fusion stage targeted is elusive, because if proteins are mobile it is not rate limiting." He also notes a tantalizing analogy to prokaryotes, which use covalently cross-linked proteoglycans as a barrier, forcing bacteriophages to use injection rather than fusion mechanisms. "For a short time," he says, "our cells become prokaryotic by erecting these walls."
Reference:
Leikina, E., et al. 2005. Nat. Immunol. doi:10.1038/ni1248.(The innate immune system has the tricky )
With virus-infected cells, however, things got more interesting. Defensins did not block virus binding or endocytic uptake but did block membrane fusion. Membrane glycoproteins no longer diffused over the membrane surface.
The lack of diffusion may be the key. When a virus binds to a cell there is still a gap of 10 nm between the membranes, which can be closed only when proteins in a tiny patch happen, via random diffusion, to get out of the way. With defensins bound, suggests Chernomordik, "the proteins would not move away."
"This might be the first natural antiviral agent targeting fusion," says Chernomordik. "The fusion stage targeted is elusive, because if proteins are mobile it is not rate limiting." He also notes a tantalizing analogy to prokaryotes, which use covalently cross-linked proteoglycans as a barrier, forcing bacteriophages to use injection rather than fusion mechanisms. "For a short time," he says, "our cells become prokaryotic by erecting these walls."
Reference:
Leikina, E., et al. 2005. Nat. Immunol. doi:10.1038/ni1248.(The innate immune system has the tricky )