Navigation Links
More than a machine
Date:11/20/2012

Viruses can be elusive quarry. RNA viruses are particularly adept at defeating antiviral drugs because they are so inaccurate in making copies of themselves. With at least one error in every genome they copy, viral genomes are moving targets for antiviral drugs, creating resistant mutants as they multiply. In the best-known example of success against retroviruses, it takes multiple-drug cocktails to corner HIV and narrow its escape route.

Rather than target RNA viruses themselves, aiming at the host cells they invade could hold promise, but any such strategy would have to be harmless to the host. Now, a surprising discovery made in ribosomes may point the way to fighting fatal viral infections such as rabies.

Results were published online November 19 in Proceedings of the National Academy of Sciences.

The ribosome has traditionally been viewed as the cell's molecular machine, automatically chugging along, synthesizing proteins the cell needs to carry out the functions of life. But Amy Lee, a former graduate student in the program of virology, and Sean Whelan, HMS professor of microbiology and immunobiology, now say the ribosome appears to take a more active role, regulating the translation of specific proteins and ultimately how some viruses replicate.

The researchers were studying differences between how viruses and the host cells they infect carry out the process of translating messenger RNAs (mRNAs) into proteins. Focusing on protein components found on the surface of the ribosome, they discovered a protein that some viruses depend on to make other proteins, but that the vast majority of cellular mRNAs do not need.

Called rpL40, this ribosomal protein could represent a target for potential treatments; blocking it would disable certain viruses while leaving normal cells largely unaffected.

"Because certain viruses are very sensitive to the presence and absence of these ribosomal proteins, it might be a useful way for us to think about targeting ribosomes for therapeutic purposes from an antiviral standpoint," said Whelan. "This is a way to think about interfering with rabies virus infection. There are no therapeutics for rabies infection."

The team screened protein constituents of the ribosome to see which ones might be involved in specialized protein synthesis. Studying the vesicular stomatitis virus, a rhabdovirus in the same family as the rabies virus, they found that its mRNAs depended on rpL40 but only 7 percent of host-cellular mRNAs did. Some of the cellular mRNAs that depend upon rpL40 were stress response genes.

Experiments in yeast and human cells revealed that a class of viruses, which includes rabies and measles, depended on rpL40 for replication.

"This work reveals that the ribosome is not just an automatic molecular machine but instead also acts as a translational regulator," said first author Amy Lee, who is now a post-doctoral researcher at the University of California, Berkeley.

The concept of targeting cellular functions such as protein synthesis for antiviral therapies is being explored by a number of research groups, but there are no drugs based on this.

"We think the principle is bigger than just this single protein," Whelan said. "Viruses have an uncanny way of teaching us new biology all the time."


'/>"/>
Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

Related biology news :

1. These bots were made for walking: Cells power biological machines
2. New brain-machine interface moves a paralyzed hand
3. IU biologists offer clearer picture of how protein machine systems tweak gene expression
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/3/2017)... WASHINGTON , April 3, 2017 /PRNewswire-USNewswire/ ... single-cell precision engineering platform, detected a statistically ... cell product prior to treatment and objective ... highlight the potential to predict whether cancer ... prior to treatment, as well as to ...
(Date:3/29/2017)... -- higi, the health IT company that operates the largest ... , today announced a Series B investment from BlueCross ... new investment and acquisition accelerates higi,s strategy to create ... health activities through the collection and workflow integration of ... and secures data today on behalf of over 36 ...
(Date:3/24/2017)... 24, 2017 Research and Markets has announced ... Analysis & Trends - Industry Forecast to 2025" report to ... The ... a CAGR of around 15.1% over the next decade to reach ... analyzes the market estimates and forecasts for all the given segments ...
Breaking Biology News(10 mins):
(Date:6/20/2017)... ... 20, 2017 , ... CTNext , Connecticut’s go-to resource ... a Higher Education Entrepreneurship Advisory Committee to implement the recommendations of the master ... representatives from 35 higher education institutions across the state over the past six ...
(Date:6/20/2017)... Pa. , June 20, 2017  Kibow Biotech ... pleased to announce the issuance of a new patent ... or hyperuricemia by the U.S. Patent and Trademark Office ... a winner of the Buzz of Bio award in ... is akin to developing non-drug approaches to chronic disease. ...
(Date:6/20/2017)... ... June 20, 2017 , ... GigaGen Inc ... millions-diverse immune repertoires, announces launch of its new Surge(TM) Discovery service ... CEO of GigaGen, will present on Surge at the conference. , Surge is ...
(Date:6/19/2017)... ... June 19, 2017 , ... Tunnell Consulting has been ... One of the biggest challenges faced by life sciences, biotech and pharmaceuticals companies today ... is Kati Abraham , who is well known in the industry and brings ...
Breaking Biology Technology: