February 12, 2013
New Study May Lead To The Development Of Broad Spectrum Antivirals
Jason Pierce, MSN, MBA, RN for redOrbit.com — Your Universe Online
A study by a team of UCLA-led researchers, published in the journal Immunity in January 2013, may aid in the development of broad spectrum medications aimed at combating existing and newly emerging viral threats. Broad spectrum antivirals can be used to treat diseases caused by a variety of different viruses. The development of these medications is a domestic biodefense goal of the National Institute of Allergy and Infectious Diseases (NIAID).
Once inside a host, viruses attach to the outside of a cell wall and implant genetic material, in the form of nucleic acid, into the cell. This genetic material contains instructions that reprogram the cell to replicate the virus. One cell can produce hundreds of thousands of viruses before being destroyed by the process. The new viruses will then attempt to attach to other healthy cells to begin the process again. In this manner, the virus moves through the host destroying cells as it reproduces.
The researchers found an oxidized derivative of cholesterol called 25-hydroxycholesterol (25HC) infuses cell walls and prevents viruses from implanting genetic material into the cell. The virus is unable to reproduce without access to the cellular machinery, and the healthy cell is not infected.
The process of converting cholesterol to 25HC is carried out by an enzyme known as cholesterol-25-hydroxylase (CH25H). The CH25H enzyme is activated by a chemical called interferon, which is released by cells in response to an attack by a foreign body. Scientist have known for some time that interferon initiates a number of important defense mechanisms within the body, but according to lead author Su-Yang Liu, a medical student at UCLA, this research is the first to describe how interferon acts to prevent a virus from entering a cell. Lu worked with principal investigator Genhong Cheng, a professor of microbiology, immunology and molecular genetics.
The research involved implanting 25HC into cell cultures, and attempting to infect the cells with Human Immunodeficiency Virus (HIV). The 25HC stopped HIV from entering the cells in the test samples. Other test samples demonstrated an inhibition of dangerous viruses, including Ebola, Nipah, and the Rift Valley fever virus.
In vivo testing, using human tissue implanted in mice infected with HIV, showed significant reduction in viral load within seven days. Researchers also found mice depleted of CH25H were more likely to become infected with other viruses.
Liu hopes the study will lead to further research into membrane-modifying cholesterols that inhibit viral reproduction. "Antiviral genes have been hard to apply for therapeutic purposes because it is difficult to express genes in cells," said Liu. "CH25H, however, produces a natural, soluble oxysterol that can be synthesized and administered.”
Liu does points out 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.
Further research is also needed to compare 25HC's antiviral effect to existing HIV antivirals.