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Cold Virus Found To Manipulate Genes

Shiloh

Editor, Senior Moderator
Source: http://www.sciencedaily.com/releases/2008/10/081024084206.htm

Cold Virus Found To Manipulate Genes

ScienceDaily (Oct. 24, 2008) ? Sneezing, runny nose and chills? You might blame the human rhinovirus (HRV), which causes 30 to 50 percent of common colds. But in reality, it's not the virus itself but HRV's ability to manipulate your genes that is the true cause of some of the most annoying cold symptoms.

For the first time, researchers have shown that HRV hijacks many of your genes and causes an overblown immune response that ends up with your nose being overblown.

The research is the first study to comprehensively review gene changes caused by HRV.

"The study's findings are a major step toward more targeted cold prevention and treatment strategies while also serving as a valuable roadmap for the broader respiratory science community,"
said David Proud, PhD, a professor in the Department of Physiology and Biophysics at the University of Calgary, and lead author of the study. The study was done in collaboration with scientists at the University of Virginia and the Procter & Gamble Company.

Proud added that while colds are usually considered to be minor infections of the nose and throat, they can have much more serious health repercussions. "Rhinovirus is the major cause of the common cold, but it is also an important pathogen in more serious conditions, such as asthma and chronic obstructive pulmonary disease (COPD)," he said.

"Advances in our understanding of the biology of the common cold may eventually lead to improvements in treatment or methods for prevention of colds," said Dr. Ron Turner, of the University of Virginia, one of the study's authors.

The researchers recruited volunteers who were inoculated with either HRV or a sham inoculation and obtained cell scrapings from the nasal passages 8 and 48 hours after inoculation and assessed the genetic changes by microarray, also know as gene chip technology.

After 8 hours, there were virtually no differences between the control and the HRV-inoculated group, but by the 48-hour mark, more than 6500 genes has been significantly up- or down-regulated in the HRV subjects?many of the more highly up-regulated genes fell into two major categories: genes making antiviral proteins, including viperin; or genes making pro-inflammatory cytokines.

"This is the first comprehensive picture to identify several groups of genes that are likely to contribute to the pro-inflammatory and antiviral response," said Dr. Proud.

The researchers also found that viral titer more than doubled in cells that had had the viperin-producing gene "knocked down," showing that HRV replication was hampered by viperin. "This had never been examined during rhinovirus infections," said Dr. Proud. "Some evidence existed that this protein (only discovered a few years ago) had effects on influenza, but nothing was known about its role in rhinovirus infections. So it was a bit unexpected."

"Overall these data provide new insights into the host response to HRV infection and identify several novel candidate genes that require further study to clarify their role in disease pathogenesis," said Dr. Proud. "This may identify proinflammatory, or host defense pathways that could be targeted for drug development, not only as treatments for colds but also for viral exacerbations of asthma and COPD.

The fact that genes associated with structural 'remodeling' or the airways were also altered, supports further study of the role of rhinovirus infections in airway remodeling in asthma."

Journal reference:

1. Proud et al. Gene Expression Profiles during In Vivo Human Rhinovirus Infection: Insights into the Host Response. American Journal of Respiratory and Critical Care Medicine, 2008; 178 (9): 962 DOI: 10.1164/rccm.200805-670OC

Adapted from materials provided by American Thoracic Society, via EurekAlert!, a service of AAAS.
 
Re: Cold Virus Found To Manipulate Genes

what do they mean with "genes were altered" ?

HRV injects own genetical material into human DNA or RNA
which then produce new proteins ?
 
Re: Cold Virus Found To Manipulate Genes

You re right.. this sentence could have the signification that virus play a role in airway remodeling asthma ?
 
Re: Cold Virus Found To Manipulate Genes

AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject
Understanding of the pathogenesis of rhinovirus infections, and of rhinovirus-induced exacerbations of asthma and chronic obstructive pulmonary disease is incomplete.

What This Study Adds to the Field
Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.

Published ahead of print on July 24, 2008, doi:10.1164/rccm.200805-670OC

Gene Expression Profiles during In Vivo Human Rhinovirus Infection
Insights into the Host Response

David Proud1, Ronald B. Turner2, Birgit Winther3, Shahina Wiehler1, Jay P. Tiesman4, Tim D. Reichling4, Kenton D. Juhlin4, Andy W. Fulmer4, Begonia Y. Ho4, Amy A. Walanski4, Cathy L. Poore5, Haruko Mizoguchi5, Lynn Jump5, Marsha L. Moore5, Claudine K. Zukowski5 and Jeffrey W. Clymer5
1 Department of Physiology and Biophysics, University of Calgary, Calgary, Canada; 2 Department of Pediatrics and 3 Department of Otolaryngology, University of Virginia, Charlottesville, Virginia; 4 Miami Valley Innovation Center, Procter & Gamble Company, Cincinnati, Ohio; and 5 Mason Business Center, Procter & Gamble Company, Mason, Ohio


Rationale: Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases.

Objectives: To define changes in gene expression profiles during in vivo rhinovirus infections.

Methods: Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections.

Measurements and Main Results: Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells.

Conclusions: Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.

Key Words: epithelial cells ? antiviral ? chemokines ? intracellular signaling proteins
http://ajrccm.atsjournals.org/cgi/content/abstract/178/9/962
 
Re: Cold Virus Found To Manipulate Genes

> 11887 gene transcripts were significantly altered in scrapings

what are gene transcripts , how were they altered , how to translate "scrapings"

> alters the expression of many genes

how are genes expressed ? Is it the proteins made from the genes ?
Can this be altered without altering the genes themselves ?
 
Re: Cold Virus Found To Manipulate Genes

*Scrapings* is likely another word for samples and indicates how the sample is taken.
Typically a scraping is done with a medical instrument pulled against the skin in the area where the infection is.
 
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