Using TRIM5α as an HIV therapeutic: the alpha gene?

As HIV continues to spread worldwide, new therapies which have the potential to treat and cure infected patients need to be developed. The results observed with the "Berlin patient" who received a bone marrow transplant with HIV-resistant hematopoietic stem cells highlight the potential of HIV gene therapy to be used as an alternative treatment. With the discovery of TRIM5α, an HIV inhibitor and species-specific restriction factor, a new molecule can be evaluated as an HIV gene therapeutic. Nonhuman primate TRIM5α orthologs restrict HIV infection, whereas human TRIM5α does not. However, upon genetic modification, variations to human TRIM5α have been made which are capable of potent HIV restriction.

This review seeks to cover the discovery and biology of various HIV-restrictive nonhuman primate TRIM5α orthologs, modifications made to human TRIM5α to enable HIV restriction, and the use of these molecules in an HIV gene therapy setting.

Engineered human TRIM5α molecules, demonstrated to be strong inhibitors of HIV infection, have the potential of being used as new HIV therapeutics in human gene therapy clinical trials. By combining TRIM5α with other highly potent anti-HIV molecules, the generation of an HIV-resistant immune system and potential cure for infected patients may be accomplished.