Newly identified protein could be used to fight HIV and other deadly viruses
Washington, Feb. 12 : A new protein has been identified that has broad virus-fighting properties which potentially could be used as a weapon against deadly human pathogenic viruses like HIV, Ebola, Rift Valley Fever, Nipah and others designated "priority pathogens."
The team of UCLA-led researchers described the antiviral property of the protein, cholesterol-25-hydroxylase (CH25H), an enzyme that converts the cholesterol to an oxysterol called 25-hydroxycholesterol (25HC), which can permeate a cell's wall and block a virus from getting in.
Working with Jerome Zack, a professor of microbiology, immunology and molecular genetics and an associate director of the UCLA AIDS Institute, the researchers initially found that 25HC dramatically inhibited HIV in cell cultures.
Next, they administered 25HC in mice implanted with human tissues and found that it significantly reduced their HIV load within seven days. The 25HC also reversed the T-cell depletion caused by HIV.
The researchers found that by contrast, mice that had the CH25H gene knocked out were more susceptible to a mouse gammaherpes virus.
In collaboration with Dr. Benhur Lee, a professor of pathology and laboratory medicine and a member of the UCLA AIDS Institute, the scientists discovered that 25HC inhibited HIV entry into the cell.
Furthermore, in cell cultures, it was found to inhibit the growth of other deadly viruses, like Ebola, Nipah and the Rift Valley Fever virus.
Intriguingly, CH25H expression in cells requires interferon, which for more than 60 years has been known to be a critical part of the body's natural defense mechanism against viruses, the protein itself does not have any antiviral properties. Rather, it triggers the expression of many antiviral genes.
Lead author Su-Yang Liu, a student in the department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA noted some weaknesses in the research. For instance, 25HC is difficult to deliver in large doses, and its antiviral effect against Ebola, Nipah and other highly pathogenic viruses have yet to be tested in vivo. Also, the researchers still need to compare 25HC's antiviral effect against other HIV antivirals.
The study has been published in the January issue of the journal Immunity.