Mice made to host HIV

A human protein allows virus replication in mouse cells.

30 June 2003

HANNAH HOAG

Mice have been off-limits to HIV researchers to date. © alamy.com

Adding a crucial human protein to mice cells allows them to carry HIV. Genetically engineered mice might one day replace the monkeys and apes used to study AIDS in the laboratory.

Experiments with mice form the cornerstone of most medical research. They share about 80% of our genes and are cheap, easy to care for and breed well in captivity. But they have been off-limits to HIV researchers. The virus, which multiplies rapidly in human cells or monkeys won't even infect mice.

Researchers know that adding a number of human proteins to the surface of mouse cells allows HIV to infect them, but no one has been able to entice the virus back out - a necessary step in the life cycle of the virus.

Virologist Yong-Hui Zheng and colleagues at the University of California, San Francisco, have identified another human protein, called hp32, that does just that¹. "We have solved a piece of the puzzle," Zheng says.

When hp32 is added to the mix of human proteins, HIV can complete a full replication cycle in the mouse cells. Zheng's team have overcome a major hurdle, but they aren't in the home stretch yet, admits Zheng.

The virus reproduces about 50-times less efficiently in mouse than in human cells. Zheng suspects there is another human protein or factor that must be expressed to get full virus production in the mouse cells.

Yet this level of manipulation may make the mouse a less than perfect model, says HIV vaccine researcher Gary Nabel, of the US National Institute of Allergy and Infectious Diseases. "It has been adapted so much that extrapolating it to the human disease is something of a risky proposition."

But even a highly modified mouse model for HIV is far from useless. "You can understand replication and do some nice immunology research," says Nabel.

Without hp32 for example, incomplete copies of HIV's genetic material accumulate in the mouse cell's nucleus - a process called over-splicing. Before Zheng's team identified hp32's role, the only way to get the cells to produce full-length pieces of viral code and transport it out of the nucleus was to introduce human chromosome 11 into the cells. The newly engineered mouse cells can produce complete sequences themselves.

"The research says a lot about the differences between mice and humans," says Nabel. "It's informative to know that this splicing step is important to HIV infection."

1. Zheng, Y., Yu, H. & Peterlin, B. M. Human p32 protein relieves a post-transcriptional block on HIV replication in murine cells. Nature Cell Biology, 5, 611 - 618, (2003). |Article|