Navigation Links
To drive infections, a hijacking virus mimics a cell's signaling system

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
Children's Hospital of Philadelphia

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:
(Date:11/10/2015)... About signature verification Signature ... identify and verify the identity of an individual ... secure and accurate method of authentication and is ... because each individual,s signature is highly unique. Signature ... signature of an individual is compared and matched ...
(Date:11/2/2015)...  SRI International has been awarded a contract of ... to the National Cancer Institute (NCI) PREVENT Cancer Program ... modern testing and support facilities, and analytical instrumentation to ... studies to evaluate potential cancer prevention drugs. ... Drug Development Program is an NCI-supported pipeline to bring ...
(Date:10/29/2015)... , Oct. 29, 2015  Rubicon Genomics, ... for U.S. distribution of its DNA library preparation ... and Rubicon,s new ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq ... the preparation of NGS libraries for liquid biopsies--the ... diagnostic and prognostic applications in cancer and other ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... The United ... recipient of the 2016 USGA Green Section Award. Presented annually since 1961, the USGA ... his or her work with turfgrass. , Clarke, of Iselin, N.J., is ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... maintain healthy metabolism. But unless it is bound to proteins, copper is also ... Health (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a systematic study ...
(Date:11/24/2015)... India , November 24, 2015 ... a new market research report "Oligonucleotide Synthesis Market by ... Application (PCR, Gene Synthesis, Diagnostic, DNA, RNAi), End-User (Research, ... 2020", published by MarketsandMarkets, the market is expected to ... Million in 2015, at a CAGR of 10.1% during ...
(Date:11/24/2015)... November 24, 2015 --> ... research report released by Transparency Market Research, the global ... a CAGR of 17.5% during the period between 2014 ... - Global Industry Analysis, Size, Volume, Share, Growth, Trends ... prenatal testing market to reach a valuation of US$2.38 ...
Breaking Biology Technology: