Featured Research

from universities, journals, and other organizations

Viruses' copying mechanism demystified, opening the door to new vaccine strategies

Date:
July 19, 2012
Source:
Penn State
Summary:
Certain kinds of viruses such as those that cause the common cold and hepatitis, copy themselves using a unique mechanism, according to scientists. The discovery sheds light on a never-before-understood region of an enzyme associated with the process of replicating genetic material. The research is an important step toward designing vaccines against viruses that have eluded vaccination strategies in the past, and improving existing vaccines.

Motif D has been identified as part of the mechanism by which genetic material is replicated accurately. The image shows how motif D identifies nucleotides to make sure that a new strand of RNA is replicated faithfully.
Credit: Boehr lab, Penn State University

Certain kinds of viruses such as those that cause the common cold, SARS, hepatitis, and encephalitis, copy themselves using a unique mechanism, according to a team of Penn State scientists that includes David Boehr, an assistant professor of chemistry and a co-leader of the research team. The discovery sheds light on a previously identified, but never-before-understood region of an enzyme associated with the process of replicating genetic material. The research is an important step toward the improvement of existing vaccines, as well as toward the design of vaccines against viruses that have eluded vaccination strategies in the past.

The research will be published in the print issue of the journal Structure on Sept. 5.

All organisms use enzymes called polymerases to "read" and copy their genetic material. While the genetic material of viruses that cause diseases such as SARS, influenza, and polio is composed of single-stranded RNA, the genetic material of many other viruses, such as those that cause herpes and conjunctivitis, is composed of double-stranded DNA. Regardless of whether the genetic material is DNA or RNA, viruses hijack a host cell's machinery, forcing it to replicate the virus's own genetic material and, ultimately, to make copies of the virus that will spread to and infect other cells.

The polymerases of many organisms, including DNA viruses, are known to have a "cupped right hand" structure -- a configuration of atoms that can be described as resembling a palm, fingers and thumb.

"We've known for some time that, in organisms that use DNA as their genetic material, within the 'palm' of the hand is specific helical structure where much of the enzyme action takes place. This 'fidelity' helix is where nucleotides -- molecules that join to form RNA and DNA -- are recognized and copied," Boehr said. "However, the polymerases of RNA viruses do not have this helix structure. Instead, the 'cupped hand' holds a different structure -- a loop known as motif D. Until now, the function of motif D was a mystery."

To unravel the mystery of motif D's function, Boehr and his colleagues studied a strain of the poliovirus -- an RNA virus that is similar to many other RNA viruses that affect humans. Using a technique called nuclear magnetic resonance spectroscopy, a process that probes the physical and chemical properties of atoms to determine the structure of organic compounds, they found that motif D is the functional equivalent of the helix structure found in the polymerases of other viruses. "Previously, it was assumed that motif D had no function at all or that it provided some sort of scaffolding to support the cupped palm structure," Boehr said. "But we have found that it is responsible for identifying nucleotides and making sure that a new strand of RNA is replicated faithfully, with as few mistakes as possible."

Boehr explained that what he and his team discovered about motif D's function in the polio strain is applicable to many other RNA viruses such as the common cold. In addition, motif D may function similarly in retroviruses -- viruses such as HIV that are replicated using an enzyme called reverse transcriptase to produce DNA from RNA genomes. "Additional studies will be necessary to confirm that motif D's role is of equal importance in retroviruses," Boehr said.

Boehr and his collaborators hope that motif D might provide a new direction for vaccine research. "Now that motif D has been identified as part of the mechanism by which genetic material is replicated accurately, it might be possible to use that information to create safer and more-efficient vaccines," Boehr said.

He explained that a vaccine, which is a weakened or harmless version of a virus, works by giving the vaccinated person's immune system a "picture" of the enemy. Once the immune system knows what the virus looks like, it can recognize and defend against the pathogen when it comes into contact with the wild, harmful version.

But one concern of this strategy is the possibility that a weakened, vaccine version of a virus might evolve once it has been introduced into a population, eventually reverting back to a wild type and becoming harmful again.

"Ideally, every copy a vaccine virus makes of itself inside human cells will be the original, lab-created, harmless version," Boehr said. "So by fine-tuning motif D; that is, by making this fidelity mechanism even more faithful, it might be possible to reduce the chances that the vaccine version of the virus will mutate and evolve on its own."

Boehr added that the research also might provide a new strategy to design vaccines for some of the RNA viruses for which vaccines have not yet been developed.

In addition to Boehr, other scientists who contributed to the research include Xiaorong Yang, David Lum, and Jesse L. Welch from Penn State's Department of Chemistry; and Eric D. Smidansky, Kenneth R. Maksimchuk, Jamie J. Arnold, and Craig E. Cameron from Penn State's Department of Biochemistry and Molecular Biology.

The research is supported, in part, by the National Institutes of Health.


Story Source:

The above story is based on materials provided by Penn State. Note: Materials may be edited for content and length.


Cite This Page:

Penn State. "Viruses' copying mechanism demystified, opening the door to new vaccine strategies." ScienceDaily. ScienceDaily, 19 July 2012. <www.sciencedaily.com/releases/2012/07/120719132858.htm>.
Penn State. (2012, July 19). Viruses' copying mechanism demystified, opening the door to new vaccine strategies. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2012/07/120719132858.htm
Penn State. "Viruses' copying mechanism demystified, opening the door to new vaccine strategies." ScienceDaily. www.sciencedaily.com/releases/2012/07/120719132858.htm (accessed April 24, 2014).

Share This



More Plants & Animals News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Monkeys Are Better At Math Than We Thought, Study Shows

Monkeys Are Better At Math Than We Thought, Study Shows

Newsy (Apr. 23, 2014) A Harvard University study suggests monkeys can use symbols to perform basic math calculations. Video provided by Newsy
Powered by NewsLook.com
Raw: Leopard Bites Man in India

Raw: Leopard Bites Man in India

AP (Apr. 22, 2014) A leopard caused panic in the city of Chandrapur on Monday when it sprung from the roof of a house and charged at rescue workers. (April 22) Video provided by AP
Powered by NewsLook.com
Iowa College Finds Beauty in Bulldogs

Iowa College Finds Beauty in Bulldogs

AP (Apr. 22, 2014) Drake University hosts 35th annual Beautiful Bulldog Contest. (April 21) Video provided by AP
Powered by NewsLook.com
805-Pound Shark Caught Off The Coast Of Florida

805-Pound Shark Caught Off The Coast Of Florida

Newsy (Apr. 22, 2014) One Florida fisherman caught a 805-pound shark off the coast of Florida earlier this month. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins