U.S. scientists led by Prof Genhong Cheng of the University of California Los Angeles have identified a natural protein with broad virus-fighting properties that could be used against deadly pathogenic viruses such as HIV, Ebola, Rift Valley Fever, Nipah and others.
Their study, published in the journal Immunity, describes the novel antiviral property of cholesterol-25-hydroxylase (CH25H), an enzyme that converts cholesterol to an oxysterol called 25-hydroxycholesterol (25HC), which can permeate a cell’s wall and block a virus from getting in.
“Interestingly, the CH25H enzyme is activated by interferon, an essential antiviral cell-signaling protein produced in the body,” said co-author Su-Yang Liu, a student at the Department of microbiology, immunology and molecular genetics at the UCLA’s David Geffen School of Medicine. “Antiviral genes have been hard to apply for therapeutic purposes because it is difficult to express genes in cells. CH25H, however, produces a natural, soluble oxysterol that can be synthesized and administered. Also, our initial studies showing that 25HC can inhibit HIV growth in vivo should prompt further study into membrane-modifying cholesterols that inhibit viruses.”
“The discovery is particularly relevant to efforts to develop broad-spectrum antivirals against an increasing number of merging viral pathogens.”
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.
By contrast, mice that had the CH25H gene knocked out were more susceptible to a mouse gammaherpes virus.
The team then found that 25HC inhibited HIV entry into the cell. Furthermore, in cell cultures, it was found to inhibit the growth of other deadly viruses, such as Ebola, Nipah and the Rift Valley Fever virus.
“Intriguingly, CH25H expression in cells requires interferon. While interferon has been known for more than 60 years 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.”
“While other studies have identified some antiviral genes that are activated by interferon, this research gives the first description of an interferon-induced antiviral oxysterol through the activation of the enzyme CH25H. It provides a link to how interferon can cause inhibition of viral membrane fusion,” Liu said.
Bibliographic information: Su-Yang Liu et al. 2012. Interferon-Inducible Cholesterol-25-Hydroxylase Broadly Inhibits Viral Entry by Production of 25-Hydroxycholesterol. Immunity, volume 38, issue 1, 92-105; doi: 10.1016/j.immuni.2012.11.005