Scientists now understand how the TRIM5 protein works and particularly how it temporarily blocks spread of the retrovirus in humans. While it was already known that this protein plays a decisive role in HIV inhibition, the research of Professor Luban, University of Geneva, precisely revealed how it operates. Published today, these results are critical in the search for an effective therapeutic solution to HIV.
When a person is infected with HIV, in many cases, it takes several years for the virus to spread in his cells and develop into a disease: AIDS, or the Acquired Immunodeficiency Syndrome. For Jeremy Luban, from the Department of Microbiology and Molecular Medicine, at the University of Geneva, this "delay", which lasts ten years on average, could be the result of the human body’s innate immune response to the intruding virus and, more specifically, can be traced to the role played by the TRIM5 protein in this context.
A pattern recognition receptor
The researcher and his group have thus brought to light the fact that TRIM5 works like a “pattern recognition receptor” that recognizes the specific behavior of the HIV retrovirus. Capable of identifying HIV’s singular structure, thanks to its specific molecular mechanisms, TRIM5 immediately alerts the innate immune system when the foreign molecule is present in the body. “We already knew that TRIM5 was the key to inhibiting HIV, but we did not know how the protein was able to identify HIV as a hazardous agent. That said, our latest research shows that TRIM5 relies on the recognition of behavior, i.e. the retrovirus’ structure, to act" explains Jeremy Luban. “The protein then attaches to the core of the virus, curbing its progress to the cell’s nucleus, the place of its potential reproduction and therefore spread of disease."
To grasp the implications of this discovery, it is necessary to place it in the continuity of HIV research and examine role that Jeremy Luban played. In fact, it was in 2004 that a PhD student in his laboratory, then located at Columbia University in New York, identified the cellular protein that, in most monkeys, blocks infection by retroviruses. The laboratory isolated this gene and tested it in human cell cultures and then in transgenic mice with the same immune characteristics as a human being infected with AIDS. This gene proved to be as active as its simian equivalent as an inhibitor of the virus’ reproduction. From then on, this protein fascinated numerous researchers (it was the subject of 300 publications in renowned scientific journals in a period of less than two years) but nobody knew how it worked.
The next steps
The results of Jeremy Luban’s research raise many new questions, starting with the difference in TRIM5’s "efficacy" between monkeys and humans. In fact, while the protein blocks spread of the virus for a long period of time in monkeys, its action is shorter in humans. “We can suppose that, in humans, TRIM5 does not sufficiently block the virus’ progress towards the cell’s nucleus due to its weak bond with the HIV core. A privileged path of investigation at the present time, for the development of a vaccine, is therefore to search for ways to strengthen this bond" declares Jeremy Luban. However, as the scientist is quick to emphasize, this objective is still quite distant and requires continued investigations into how HIV works in general and the mechanisms of TRIM5 in particular.