Featured Research

from universities, journals, and other organizations

Measles' natural nemesis: Cells infected by measles virus pull out a heavy weapon in the form of the enzyme ADAR1

Date:
January 21, 2011
Source:
Scripps Research Institute
Summary:
Scientists have found that a known enzyme in cells protects against measles virus, likely by altering the virus's genetic material, RNA. Cells lacking the enzyme become highly vulnerable to the virus's destructive effects. The enzyme also protects against several other respiratory viruses, including influenza A.

Scientists at The Scripps Research Institute have found that a known enzyme in cells protects against measles virus, likely by altering the virus's genetic material, RNA. Cells lacking the enzyme become highly vulnerable to the virus's destructive effects. The enzyme also protects against several other respiratory viruses, including influenza A.

"We believe that host cells use this RNA-editing enzyme to slow these viruses' ability to replicate," said Michael B. A. Oldstone, the study's senior author and a professor at Scripps Research's La Jolla, California campus. The study's first authors are Simone V. Ward, a senior research associate in the Scripps Research Oldstone laboratory, and Cyril X. George of the University of California, Santa Barbara.

The finding represents a significant improvement in the understanding of measles infections, which still kill about 150,000 children and adults around the world every year. The paper, which was published recently in Proceedings of the National Academy of Sciences, has prompted commentaries in the journals Nature Reviews Microbiology and Viruses.

The focus of the study was the enzyme ADAR1 ("adenosine deaminase acting on RNA, 1"), which is known to be produced in high amounts in measles-infected cells. ADAR1 has been suspected as a "restriction factor" that inhibits viral replication.

ADAR1's role against measles has been difficult to nail down, however. In mice genetically engineered to be infectable by measles -- a virus that normally infects only humans -- ADAR1 is required for embryonic development, as in all mice. Thus the standard "gene knockout" technique, which would enable scientists to see how measles infections proceed without ADAR1, hasn't been feasible.

In this study, Ward, George, and Oldstone, and their colleagues knocked out only one of the two forms of ADAR1 produced in cells. This form, p150, is the one produced in response to infections. For reasons that still aren't clear, mouse embryos cannot grow for long without p150, so the researchers used a standard technique to "immortalize" these p150-knockout embryonic cells -- ensuring their continuous supply -- and in this way created a useful cell model.

When infected by measles virus, the p150-knockout cells succumbed quickly compared to immortalized control cells that produced p150 normally. "When I looked at the cells only 21 hours after infection, the p150-knockout cells already showed the signs of cell damage typical of measles infection," said Ward. "But the control cells looked exactly like uninfected cells."

In further tests, Ward found p150 also provided significant protection for cells against Newcastle disease virus, Sendai virus, canine distemper virus, and influenza A virus -- which are all respiratory viruses like measles, and all members of the paramyxovirus or orthomyxovirus families.

Nine years ago, it was reported that a cellular enzyme known as APOBEC3G protects cells from DNA-based viruses such as HIV, by mutating viral genes. "We're now showing that an analogous gene-editing enzyme also seems to exist for RNA viruses," said Oldstone.

With the new cell model, and advanced "conditional knockout" techniques that allow genes to be disrupted in specific organs in adult mice, Ward, Oldstone, and their colleagues now hope to study ADAR1-p150's role in more detail.

One key issue to be resolved is the enzyme's role during brain infections. Measles virus usually results in a relatively mild illness lasting only a week or two, but in rare cases it spreads to the brain and becomes a persistent, always fatal infection known as subacute sclerosing panencephalitis (SSPE). In such cases, the virus doesn't have to spread via cell-to-cell contact, thus exposing itself to the immune system; it can spread more stealthily along the axons and dendrites that connect neurons.

"What we hope to show with our ongoing work is that host neurons are using ADAR1 to slow down this process, turning it into a gradual neurological disease," said Oldstone. ADAR1 might also be exacerbating the neurological symptoms of SSPE, he adds, because its enzymatic activity is known to affect the production of the important neurotransmitter receptors for serotonin and glutamate: "It's an enzyme that has multiple roles," Oldstone concluded.


Story Source:

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


Journal Reference:

  1. S. V. Ward, C. X. George, M. J. Welch, L.-Y. Liou, B. Hahm, H. Lewicki, J. C. de la Torre, C. E. Samuel, M. B. Oldstone. RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis. Proceedings of the National Academy of Sciences, 2010; 108 (1): 331 DOI: 10.1073/pnas.1017241108

Cite This Page:

Scripps Research Institute. "Measles' natural nemesis: Cells infected by measles virus pull out a heavy weapon in the form of the enzyme ADAR1." ScienceDaily. ScienceDaily, 21 January 2011. <www.sciencedaily.com/releases/2011/01/110120125003.htm>.
Scripps Research Institute. (2011, January 21). Measles' natural nemesis: Cells infected by measles virus pull out a heavy weapon in the form of the enzyme ADAR1. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2011/01/110120125003.htm
Scripps Research Institute. "Measles' natural nemesis: Cells infected by measles virus pull out a heavy weapon in the form of the enzyme ADAR1." ScienceDaily. www.sciencedaily.com/releases/2011/01/110120125003.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) Video provided by AP
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