平特五不中

Could lead to treatments to block commandeering of cell鈥檚 internal 鈥渉ighway鈥�

Researchers at 平特五不中 and the affiliated Lady Davis Institute for Medical Research at Montreal鈥檚 Jewish General Hospital 鈥撀� along with colleagues at the University of Manitoba and the University of British Columbia 鈥� may have found a chink in the armour of the human immunodeficiency virus type 1 (HIV-1), the microorganism which causes AIDS. They have pinpointed the key cellular machinery co-opted by HIV-1聽 to hijack the human cell for its own benefit. Their study was published in May in the Journal of Biological Chemistry.

Once a cell is infected with HIV-1, activation of the virus鈥檚 gene generates a large HIV-1 RNA molecule known as the RNA genome. This is then transported from the cell nucleus to the inner surface of the plasma membrane. The RNA genome can produce both structural proteins and enzymes, but once it arrives at the plasma membrane it can also assemble into new copies of the virus that actually bud out of the cell. Dr. Andrew J. Mouland and his colleagues have discovered how the RNA genome gets transported 鈥� or trafficked 鈥� from the nucleus to the plasma membrane.

鈥淭here is a highway inside the human cell,鈥� explained Dr. Mouland, Associate Professor at 平特五不中鈥檚 Departments of Medicine and聽 Microbiology and Immunology and head of the HIV-1 RNA Trafficking Laboratory at the Lady Davis Institute. 鈥淲hen you drive your car to Toronto you鈥檙e 鈥榯rafficking鈥� the items in your trunk. Similarly, what we have shown is that HIV-1 commandeers the host cell鈥檚 endosomal machinery to traffic its structural proteins and RNA genome. Imagine that it鈥檚 essentially jumping on board for the ride and directing it to where it needs to go. This trafficking can occur very fast in cells; so this is how these key components of HIV-1 so efficiently get to the plasma membrane, where the virus can begin to assemble.

鈥淭he RNA genome is critical, because if it doesn鈥檛 get trafficked to the right place at the plasma membrane, the virus will not be infectious,鈥� he explained.

This discovery is extremely exciting, Dr. Mouland said, because now that researchers understand a little more about how the cell鈥檚 transport machinery is hijacked by HIV-1, they have hopes that they can now begin to devise strategies to block the process.

This work is substantiated by a co-submitted manuscript from the group of 脡douard Bertrand at the Institut de g茅n茅tique mol茅culaire de Montpellier, Centre national de recherche scientifique. The Bertrand group will publish its work in the same journal in June, 2009.