Navigation Links
Herpes virus hijacks DNA repair process

June 13, 2007 -- Scientists probing the details of viral infection have discovered an intriguing surprise: in mice, herpes viruses hijack their host cells' tools for fixing DNA damage and use those tools to enhance their own reproduction.

The DNA damage response normally fixes DNA errors caused by radiation or other environmental factors, or mistakes accidentally introduced when cells copy their genetic material prior to dividing.

In the murine (or mouse-infecting) herpes virus they studied, researchers at Washington University School of Medicine in St. Louis identified a protein that can trick the mouse cell into turning on the DNA damage response. They also showed that Epstein-Barr virus, a human herpes virus, has a similar protein. Scientists found that blocking murine herpes virus from activating the DNA damage response caused viral replication rates to plummet.

"We don't want to treat viral infection by blocking DNA damage response systemically because this process is used constantly throughout the body and is very important to preventing cancer," says lead author Vera Tarakanova, Ph.D., a postdoctoral fellow. "However, by targeting the viral protein responsible for activating the DNA damage response, we may be able to block viral replication. In addition, determining how the DNA repair response helps viral replication may enable us to develop novel strategies to treat infection."

The paper appears online this week in Cell Host & Microbe. Scientists have known for some time that viral infection of cells activates the DNA damage response. But researchers had assumed that this activation occurred because repair mechanisms were mistaking replicating viral DNA for damaged or dysfunctional cellular DNA.

"Viruses sometimes structure their own DNA differently than cellular DNA," Tarakanova notes. "Many of us thought that such differences might be triggering the DNA damage response." Working in the laboratory of H erbert W. "Skip" Virgin, M.D., Ph.D., Edward Mallinckrodt Professor and head of the Department of Pathology and Immunology, Tarakanova found that murine herpes virus, rather than the host cell, was triggering the DNA damage response. She showed that introducing just one viral protein into cells led to activation of two cellular proteins involved in the damage response, ATM and H2AX.

The viral protein that triggered this inappropriate activation, orf36, is a kinase, a type of protein that chemically modifies other molecules to activate different processes or transmit signals. Genetic comparisons with several human herpes viruses revealed kinases similar to orf36 in the human viruses. Scientists then took a similar kinase from human Epstein-Barr virus and showed that introducing it into cells also activated the DNA damage response.

When the research team genetically disabled orf36 in the murine herpes virus and infected mouse cells with it, the virus no longer activated the DNA damage response. The virus's ability to replicate also dramatically decreased.

Kinases are versatile proteins that sometimes play multiple roles. To ensure that enhanced viral replication wasn't linked to orf36's interactions with other molecules, researchers turned to mice lacking the genes for ATM and H2AX, the damage response proteins activated by infection. When they infected cells from these mice with murine herpes virus, its ability to reproduce was again curtailed. How DNA damage response benefits viral replication is still a mystery and a topic of continuing investigation in the Virgin lab.

"The discovery that induction of the cells' DNA damage response is an intentional viral strategy, rather than a passive cellular response to viral invasion, means that we should look into whether other DNA viruses use a similar approach to enhance their growth," says Virgin.


'"/>

Source:Washington University School of Medicine


Related biology news :

1. Herpes infection may be symbiotic, help beat back some bacteria
2. Association of herpesvirus with lung disorder questioned
3. Topical treatment shown to inhibit HIV and herpes simplex virus infection
4. Elusive HIV shape change revealed; Key clue to how virus infects cells
5. Newly discovered virus linked to childhood lung disorders and Kawasaki disease
6. Live Recombinant Adenovirus Vaccine Technique Explored
7. Marburg virus disease in Angola - update
8. Studies reveal methods viruses use to sidestep immune system
9. Norovirus, AIDS vaccine and Hepatitis Virus
10. Epstein-Barr virus protein crucial to its role in blood cancers
11. Live vaccines more effective against horse herpes virus

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/13/2017)... According to a new market research report "Consumer IAM Market by ... Service, Authentication Type, Deployment Mode, Vertical, and Region - Global Forecast to ... USD 14.30 Billion in 2017 to USD 31.75 Billion by 2022, at ... ... MarketsandMarkets Logo ...
(Date:4/11/2017)... , April 11, 2017 NXT-ID, ... security technology company, announces the appointment of independent Directors Mr. ... to its Board of Directors, furthering the company,s corporate ... ... NXT-ID, we look forward to their guidance and benefiting from ...
(Date:4/5/2017)... KEY FINDINGS The global market for stem ... 25.76% during the forecast period of 2017-2025. The rise ... growth of the stem cell market. Download ... The global stem cell market is segmented on the ... cell market of the product is segmented into adult ...
Breaking Biology News(10 mins):
(Date:10/9/2017)... (PRWEB) , ... October 09, 2017 , ... At its ... Dr. Christopher Stubbs, a professor in Harvard University’s Departments of Physics and Astronomy, has ... was a member of the winning team for the 2015 Breakthrough Prize in Fundamental ...
(Date:10/7/2017)... ... October 06, 2017 , ... ... for microscopy and surface analysis, Nanoscience Instruments is now expanding into Analytical ... broad range of contract analysis services for advanced applications. Services will leverage ...
(Date:10/6/2017)... ... October 06, 2017 , ... ... the healthcare and technology sector at their fourth annual Conference where founders, investors, ... inspiring speakers and the ELEVATE pitch competition showcasing early stage digital health and ...
(Date:10/5/2017)... ... , ... Understanding the microbiome, the millions of bacteria that live in our ... My Future, the newest exhibit on display at the University City Science Center’s Esther ... the lens of the gut microbiome. , Gut Love opens October 12, 2017, ...
Breaking Biology Technology: