mrz
29-06-03, 18:50
Mice succumb to HIV at last
18:00 29 June 03
NewScientist.com news service
AIDS research could shift into a higher gear thanks to an advance that for the first time allows HIV to fully replicate inside mouse cells.
Researchers at the University of California, San Francisco added a human protein called hp32 to mouse cells to help HIV properly assemble its genome into viral particles. The team is now creating whole mice with the hp32 gene, and looking for other factors that enhance viral infection.
A genetically-engineered mouse model of HIV infection would vastly accelerate AIDS research because genetics and immunology are so well understood in mice. These animals, for instance, would speed the development and testing of vaccine and drugs.
"Right now chimpanzees are the major models for HIV infection," says UCSF team member Yong-Hui Zheng. "But those experiments are expensive. Few labs can keep primates and it's impossible to do the same range of experiments you can do in mice. So this is very exciting."
But Zheng cautions that even with this advance, a proper mouse model of HIV could be years away. Researchers have struggled more than a decade to make mice a suitable host for the virus.
Creating handholds
Mouse cells are naturally resistant to HIV in many ways. Some of these barriers have been overcome by adding human genes to mouse cells. Two genes, CD4 and CCR5, create "handholds" on the surface of cells that allow HIV to invade. Another, CycT1, produces a protein that helps the virus switch on its genes.
But even with those changes, the virus cannot complete its lifecycle by packaging its genome into viral particles. Zheng, with Hai-Feng Yu and Matija Peterlin, discovered this is because mouse cells process the RNA genome of HIV so quickly into smaller pieces that few full-length copies of the virus are left.
They discovered that hp32 is responsible for slowing down this process. When hp32 and the three other human co-factors were added to mouse cells, HIV was able to invade, switch on its genes and package whole genomes into infective particles.
"They have overcome a major hurdle towards making a mouse model," says Ed Berger of the US National Institute of Allergy and Infectious Diseases in Washington, DC, whose team discovered the role of the HIV cofactor CCR5.
But even though HIV can now live out its life inside the altered mouse cells, the virus still replicates 50 times more slowly in mouse cells than human cells. That suggests there must be other human proteins that boost its replication. "We already have some hints about the identity of those other molecules," says Zheng.
Journal reference: Nature Cell Biology (vol 5, p 611)
Philip Cohen
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http://www.newscientist.com/news/news.jsp?id=ns99993884
:cheefbek:
18:00 29 June 03
NewScientist.com news service
AIDS research could shift into a higher gear thanks to an advance that for the first time allows HIV to fully replicate inside mouse cells.
Researchers at the University of California, San Francisco added a human protein called hp32 to mouse cells to help HIV properly assemble its genome into viral particles. The team is now creating whole mice with the hp32 gene, and looking for other factors that enhance viral infection.
A genetically-engineered mouse model of HIV infection would vastly accelerate AIDS research because genetics and immunology are so well understood in mice. These animals, for instance, would speed the development and testing of vaccine and drugs.
"Right now chimpanzees are the major models for HIV infection," says UCSF team member Yong-Hui Zheng. "But those experiments are expensive. Few labs can keep primates and it's impossible to do the same range of experiments you can do in mice. So this is very exciting."
But Zheng cautions that even with this advance, a proper mouse model of HIV could be years away. Researchers have struggled more than a decade to make mice a suitable host for the virus.
Creating handholds
Mouse cells are naturally resistant to HIV in many ways. Some of these barriers have been overcome by adding human genes to mouse cells. Two genes, CD4 and CCR5, create "handholds" on the surface of cells that allow HIV to invade. Another, CycT1, produces a protein that helps the virus switch on its genes.
But even with those changes, the virus cannot complete its lifecycle by packaging its genome into viral particles. Zheng, with Hai-Feng Yu and Matija Peterlin, discovered this is because mouse cells process the RNA genome of HIV so quickly into smaller pieces that few full-length copies of the virus are left.
They discovered that hp32 is responsible for slowing down this process. When hp32 and the three other human co-factors were added to mouse cells, HIV was able to invade, switch on its genes and package whole genomes into infective particles.
"They have overcome a major hurdle towards making a mouse model," says Ed Berger of the US National Institute of Allergy and Infectious Diseases in Washington, DC, whose team discovered the role of the HIV cofactor CCR5.
But even though HIV can now live out its life inside the altered mouse cells, the virus still replicates 50 times more slowly in mouse cells than human cells. That suggests there must be other human proteins that boost its replication. "We already have some hints about the identity of those other molecules," says Zheng.
Journal reference: Nature Cell Biology (vol 5, p 611)
Philip Cohen
Related Stories
HIV's complex family history unravelled
12 June 2003
Rapid immune reaction key to staving off AIDS
6 October 2002
Anti-HIV blood factor unmasked
26 September 2002
http://www.newscientist.com/news/news.jsp?id=ns99993884
:cheefbek: