Gene discovery offers fresh perspective on HIV/AIDS therapies
Scientists have isolated a gene that inhibits HIV-1 infection raising hopes of a new type of natural resistance to viral activity that could be exploited in the quest for novel HIV/AIDS therapeutics.
The research, which appears on the Nature website (http://www.nature.com/nature) ahead of print publication, centres on a unique cellular gene known as CEM15, whose antiviral action is overcome by the presence of virion infectivity factor (Vif) proteins. The Vif proteins are encoded by HIV-1 and are potent regulators of viral infection and replication.
The team studied cells infected with a form of HIV that lacks Vif. They found that CEM15 interfered with the HIV life cycle, rendering any new virus particles non-infectious.
Ann Sheehy (University of Pennsylvania) et al. write: We propose that CEM15 comprises a significant part of a form of innate antiviral resistance, and suggest that relieving its suppression by Vif may lend a fresh perspective to the area of HIV/AIDS therapies.
The search for new HIV-1 targets is becoming increasingly urgent due to the rise in resistance to standard combination drug strategies. Targeting Vif, which acts at a different stage of the viral life cycle, would circumvent the problems associated with inhibitors of reverse transcriptase and protease.
Co-author Michael Malin, from Kings College London, added: These are very significant findings and could open the door to new treatments for HIV/AIDS in the future.
If we can find a way to block the action of Vif, it would allow CEM15 to work properly and prevent HIV from spreading.
The authors caution, however, that there is still much work to be done. Ongoing work includes identifying substances that bind to and inhibit Vif in the cell, elucidating its precise mechanisms of action and structural studies of the protein.
Sheehy AM, Gaddis NC, Choi JD et al. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature.