UC Irvine finds Achilles heel of virus family often implicated in ME/CFS
August 29, 2012
For ME/CFS patients especially, this may be an important finding given the body of research suggesting associations with entero-, coxackie-, and other picornavirus infections.
"The primary challenge of antiviral drug resistance may be sidestepped by targeting a newly identified host cell function required for viral replication, and not the virus itself."
By discovering how certain viruses use their host cells to replicate, University of California, Irvine microbiologists have identified a new approach to the development of universal treatments for viral illnesses ranging from meningitis, encephalitis, and hepatitis to the common cold.
The UCI researchers, working with Dutch colleagues at Leiden University, found that certain RNA viruses hijack a key DNA repair activity of human cells to produce the genetic material necessary for them to multiply.
For many years, scientists have known that viruses rely on functions provided by their host cells to increase their numbers, but the UCI study - led by microbiology & molecular genetics professor Bert Semler, PhD - is the first to identify how the RNA-containing picornaviruses utilize a DNA repair enzyme to do so.
Study results were published Aug 20 by the Proceedings of the National Academy of Sciences (PNAS) (See “An RNA virus hijacks an incognito function of a DNA repair enzyme.”)
RNA viruses have ribonucleic acid as their genetic material (rather than deoxyribonucleic acid, or DNA). Notable human diseases caused by RNA viruses include:
• Hepatitis C,
• West Nile fever,
• The common cold,
And, as noted, a great deal of research has implicated picornaviruses in 'chronic fatigue syndrome' aka ME/CFS.(1, 2)
The UCI and Dutch researchers examined the picornavirus group of RNA viruses using biochemical purification methods and confocal microscopy to see how they co-opt the functions of a cellular DNA repair enzyme called TDP2 to advance their replication process.
According to Dr. Semler, who directs UCI’s Center for Virus Research:
“These findings are significant because all known picornaviruses harbor the target for this DNA repair enzyme, despite the fact that their genetic material is made up of RNA rather than DNA.
“Thus, identifying drugs or small molecules that interfere with the interaction between the virus and TDP2 could result in a broad-spectrum treatment for picornaviruses.”
Sidestepping Problem of Viral Mutation
By targeting a host cell function required for viral replication and not the virus itself, he added, the primary challenge of antiviral drug resistance may be sidestepped.
• As part of their survival mechanism, RNA viruses mutate often, and drugs intended for them usually become ineffective over time.
• HIV, for example, rapidly mutates, necessitating a combination therapy employing a number of antiviral agents.
• A drug that blocks RNA viruses from hijacking DNA repair enzymes may avoid these resistance issues.
Dr. Semler has said that his lab now plans to screen mixtures of drug candidates to find ones that inhibit this process – starting with cells infected by the human rhinovirus, the predominant cause of the common cold. (Actually the genus Rhinovirus no longer exists, according to Picornaviridae.com. The two original human rhinovirus species have been moved to the genus Enterovirus, meaning virus that infects through a membrane, as in the gastrointestinal or respiratory tract.)
Ed Note: Increasingly, such screening tasks are aided by databases/libraries that allow rapid sifting of accumulated information about thousands of compounds and drugs, as well as by "high-throughput screening" technology for testing purposes. One such library is reportedly housed at the University of California, San Francisco, which like other emerging noncommercial drug libraries has sourced many of its compound samples from the Johns Hopkins Drug Library. The Hopkins library houses on ice more than 3,000 drugs already approved for clinical use going back a century or more.
Richard Virgen-Slane, Janet Rozovics, Kerry Fitzgerald, Tuan Ngo, Wayne Chou and Paul Gershon of UCI and Gerbrand van der Heden van Noort and Dmitri Filippov of Leiden University in the Netherlands participated in the study, which received support from the American Asthma Foundation and a National Institutes of Health Public Health Service grant.
Source: Based on University of California, Irvine press release, Aug 20, 2012.
1. "Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach," by John and Andrew Chia, Journal of Clinical Pathology, Aug 2007. They found enterovirus infection in stomach biopsies of 135 of 165 (82%) consecutive ME/CFS patients, vs. 20% of controls.
2. "Documented involvement of viruses in ME/CFS," Margaret Williams, Dec 2009.
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