Project Inform Perspectives 39 - December 2004

It’s well known that baboons and most monkeys cannot be infected with HIV, but until recently it wasn’t known why these animals are protected from HIV infection. While there are related viruses that can infect non-human primates, called simian immune deficiency virus (SIV), those viruses rarely cause disease in the animals. Researchers have recently discovered a protein that these animals produce, called Trim5-alpha. It appears to block HIV infection of cells, though has little to no effect on SIV. Humans produce a form of Trim5-alpha, but the human form does not block HIV as well as the animal form of the protein.

In research conducted at Harvard University/Dana-Farber Cancer Institute, scientists found that when they chemically blocked the animal form of Trim5-alpha, the monkey cells were infectable by HIV in test tubes. Also, adding the animal Trim5-alpha to human cells in test tubes resulted in their protection from HIV infection.

This discovery is potentially important for several reasons:

• It may lead to the development of animal models for HIV/AIDS—by blocking Trim5-alpha in monkeys and infecting the monkeys with HIV it may be possible to better study HIV/AIDS—hopefully leading to increased understanding of the disease and new and better treatments.
• It may be possible to use the discovery in gene therapy for HIV. Human cells might be modified with a gene that will enable them to produce the animal form of Trim5-alpha and thus protect cells against HIV infection.
• Human Trim5-alpha does not prevent HIV infection of cells, though human Trim5-alpha has about 80% similarity to the animal form. It might be possible to modify human Trim5-alpha so that it is more potent against HIV.
• It may represent a therapy of particular interest in vaccine/prevention research, pre- or post-exposure prevention study and for treating very early/acute HIV infection.

Trim stands for T Cell Receptor Interacting Molecule. The Trim family of genes plays a part in regulating interactions between receptors on the outside of cells and signals on the inside of cells. The discovery that this particular Trim gene may have protective effects against HIV will undoubtedly pave the path to more research on this gene family. Also, this discovery likely leads the way to identifying other animal gene/proteins that block HIV.

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