Navigation Links
To drive infections, a hijacking virus mimics a cell's signaling system
Date:3/26/2012

New biological research reveals how an invading virus hijacks a cell's workings by imitating a signaling marker to defeat the body's defenses. By manipulating cell signals, the virus destroys a defensive protein designed to inhibit it. This finding, from studies in human cell cultures, may represent a broader targeting strategy used by other viruses, and may lay the scientific groundwork for developing more effective treatments for infectious diseases.

"Learning details of how cells respond to viruses helps us to understand key cellular machinery better," said study leader Matthew D. Weitzman, Ph.D., of the Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia. "This study tells us how a virus overcomes intrinsic host defenses. In this case the virus mimics signals used during normal DNA repair mechanisms."

The study team, formerly based at the Salk Institute for Biological Studies in La Jolla, Calif., published their current findings online March 8 in Molecular Cell.

Biologists have long known that viruses hijack cellular processes to replicate themselves, while host cells have evolved intrinsic defense systems to resist viral invasion. To replicate, viruses must deliver their own DNA into a cell's nucleus, so a viral infection entails a conflict between two genomesthe DNA of the host cell versus the foreign DNA of the virus.

Viruses mount their attack by interacting with specific cell proteins as a way of penetrating the cell's defenses. "In this study, we asked how the herpes simplex virus finds the specific proteins that it interacts with," said Weitzman. "By describing the mechanism of this particular interaction between a virus and a cell protein, we have pinpointed key regulators of a cell's processes, and shed light on how a cell regulates its defenses."

This laboratory study focused on herpes simplex virus type-1 (HSV-1), a common human virus that results in recurrent infections alternating with inactive periods. Like other viruses, HSV-1 is known to manipulate cellular processes in order to infect cells, but the specific mechanisms by which it acts on the DNA repair pathway were previously unknown.

Weitzman's study team was studying a viral protein called ICP0 that overcomes host defenses by targeting cellular proteins for destruction. They found that ICP0 exploits phosphorylation, a chemical mark that is often used in cells to promote interactions between proteins, especially as part of the cellular signaling response to DNA damage. In HSV-1 infection, the phosphorylation signal on ICP0 attracts a cellular DNA damage response protein, RNF8, which binds to the false signaling marker and is then degraded. Because RNF8 normally inhibits viral replication, its destruction leaves the cell vulnerable to HSV-1 infection, as the virus takes over the cell's machinery.

The researchers also found that ICP0 exploits the same phosphorylation signal to bind to other cellular proteins in addition to RNF8, a hint that it may play a broader role in defeating antiviral defenses and manipulating cellular machinery. Weitzman will continue to investigate HSV-1 infection in neurons and in animal models. He also plans to extend his research into other viruses, which may act on different pathways than HSV-1 does. "Ultimately," he added, "better knowledge of molecular mechanisms in infection may suggest strategies to interrupt the viral life cycle and treat infections."


'/>"/>
Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

Related biology news :

1. An early spring drives butterfly population declines
2. Head-first diversity shown to drive vertebrate evolution
3. Predators drive the evolution of poison dart frogs skin patterns
4. Signaling pathway linked to inflammatory breast cancer may drive disease metastasis
5. Key driver of metastasis identified
6. Stress drives alcoholics children to drink
7. NASA study refutes claims of drought-driven declines in plant productivity, global food security
8. Climate change could drive native fish out of Wisconsin waters
9. Harmful effects of hypothyroidism on maternal and fetal health drive new guidelines for managing thyroid disease in pregnancy
10. Time to let science drive Great Lakes policy on Asian carp, experts say
11. U.S. Biomedical Leaders Present a New National Device Innovation Strategy Based on "Value-driven Engineering"
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/12/2016)... DALLAS , May 12, 2016 ... has just published the overview results from the Q1 ... of the recent wave was consumers, receptivity to a ... wearables data with a health insurance company. ... choose to share," says Michael LaColla , CEO ...
(Date:5/3/2016)... 2016  Neurotechnology, a provider of high-precision biometric ... Biometric Identification System (ABIS) , a complete system ... ABIS can process multiple complex biometric transactions with ... fingerprint, face or iris biometrics. It leverages the ... MegaMatcher Accelerator , which have been used ...
(Date:4/28/2016)... First quarter 2016:   , ... the first quarter of 2015 The gross margin was ... 18.8) and the operating margin was 40% (-13) Earnings ... flow from operations was SEK 249.9 M (21.2) , ... SEK 7,000-8,500 M. The operating margin for 2016 is ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the ... the Supplyframe Design Lab . Located in Pasadena, Calif., the Design Lab’s ... how hardware projects are designed, built and brought to market. , The Design ...
(Date:6/23/2016)... ... , ... In a new case report published today in STEM CELLS Translational ... lymphedema after being treated for breast cancer benefitted from an injection of stem cells ... this debilitating, frequent side effect of cancer treatment. , Lymphedema refers to ...
(Date:6/23/2016)... 23, 2016  Blueprint Bio, a company dedicated to ... medical community, has closed its Series A funding round, ... "We have received a commitment from Forentis ... need to meet our current goals," stated Matthew ... runway to complete validation on the current projects in ...
(Date:6/23/2016)... 23, 2016 On Wednesday, June 22, ... down 0.22%; the Dow Jones Industrial Average edged 0.27% lower ... 2,085.45, down 0.17%. Stock-Callers.com has initiated coverage on the following ... Therapeutics (NASDAQ: NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ... BIND ). Learn more about these stocks by accessing ...
Breaking Biology Technology: