(photo credit: REUTERS)
A mechanism that forms the basis of resistance of the feline immunodeficiency virus (FIV) that causes “cat AIDS” has been discovered by Associate Prof. Akram Alian and Dr. Meital Galili of the biology faculty at Haifa’s Technion-Israel Institute of Technology.
They have just published their findings in PLoS Pathogens.
Immunodeficiency in cats is caused by viruses very similar to human immunodeficiency virus – HIV-1 – that causes human AIDS. In the feline version, which is transmitted by cats via saliva, the immune system is damaged and can’t fight infections, diseases and the development of cancer cells. The disease is more common in male street cats, which tend to get into fights and bite each other.
This structure underlines the extent to which these viral proteins are subject to minimal changes that allow resistance to drugs to be developed while preserving the functionality of the protein, which has not yet been observed in HIV-1.
Although FIV virus does not infect humans, it is a disease that concerns many around the world because it harms the cats themselves. But in addition, there are many parallels with HIV.
“Through this structure, it will be possible to develop stronger and more specific drugs that will enable us to overcome the meteorological levels of the AIDS virus,” said Alian. “Of course, because of the existing parallels between FIV and HIV-1, we believe the discovery will also help fight AIDS.”
The disease develops in three stages – an acute phase characterized by fever and increased susceptibility to internal and external infections; a symptom-free latent phase during which the immune system gradually decreases and the stage of immunodeficiency, which may occur only after many years, in which the immune system is weakened to the point of being life-threatening; and the final stage, in which the cat may die from relatively simple infections that would not have harmed him if his immune system had been normal.
Despite the global fight against AIDS, this disease continues to claim many thousands of victims each year. Despite the resistance of the affected body cells and the use of targeted drugs, the HIV-1 virus can survive and reproduce in the living cell and develop increased resistance.
The power of the AIDS virus stems from the great variation in its genome, made possible by one of the proteins it produces – a reverse transcriptase protein. The viral genome is made up of RNA, but this protein can “translate” the RNA into DNA in the opposite direction from the common process in nature. FIV and HIV-1, like other retroviruses, can “plant” the same DNA in the host’s genome – that is, the infected body – causing the host cell to produce copies of the virus. Because of the importance of viral replication, this protein serves as a significant basis for the development of anti-AIDS drugs that will help overcome the various strains that viruses continue to produce.
The two Haifa researchers showed the protein structure of the cat’s virus in its three-dimensional form, thereby discovering the mechanism of resistance of the virus to drugs against reverse transcription – a mechanism based on a closed-pocket configuration that prevents the association of drugs called non-nucleoside reverse transcriptase inhibitors.