Scientists established a comprehensive protein interactions map of the replication machinery of a chronic virus

December 20, 2017, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Schematic illustration of an LCMV-Infection and the interactions of the LCMV polymerase (in violett) with cellular proteins. Credit: CeMM/Bojan Vilagos

Chronic viral infections like HIV or hepatitis are among the biggest threats to human health worldwide. While an acute viral infection usually results in full recovery and effective immune memory, chronic viruses evade the immune system and remain permanently in the host's body. Treating such viruses is a difficult task, as the molecular events during the development of a chronic infection remain largely elusive.

With their latest study published in PLOS Pathogens, the team of Andreas Bergthaler at the Austrian Academy of Sciences, in cooperation with the University of Basel and the MRC Laboratory of Molecular Biology, Cambridge, made an important contribution to the understanding of chronic viral infections. The scientists established the first comprehensive overview of cellular proteins interacting with the LCMV polymerase, a crucial enzyme for the replication of the and for chronic infection. By mapping them in the , they revealed viral strategies and potential targets for future antiviral therapeutics.

In order to perform the study, the researchers, including Ph.D. student Kseniya Khamina as first author, developed a novel approach to tag . The interactions of the LCMV polymerase with the proteins of the host cells were determined. Combined with publicly available data from other RNA viruses' polymerase interactomes, the generated dataset allowed the researchers to map the cellular pathways targeted by different viral polymerases. Some of the proteins found to interact with the LCMV polymerase turned out to be essential for the viral life cycle.

Simplified depiction of LCMV and human influenza and hepatitis C interactomes (shared. interactions highlighted in red). Credit: CeMM/Bojan Vilagos

"With our newly developed method we were able to show that some proteins, like DDX3X, have a proviral effect—they are important binding partners for the virus to survive. Others, like the TRIM21 protein, show more of an antiviral effect, they serve the host cell as an intracellular defense against the pathogen," explains Kseniya Khamina. "Mice lacking the TRIM21 entirely showed an impaired virus control when infected with a chronic strain of LCMV."

"The results of our study provide the first comprehensive overview of the molecular binding partners of the LCMV polymerase. Furthermore, their mapping in the human proteome reveals important strategies of chronic viruses," Andreas Bergthaler summarizes the findings. "We hope that our research leads to a better understanding of the emergence of and the complex molecular interactions of viruses and their hosts, and that we can thereby contribute to the development of novel antiviral therapies."

Explore further: New therapeutic target against persistent viral infections

More information: "Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein" PLOS Pathogens, December 20, 2017. DOI: 10.1371/journal.ppat.1006758

Related Stories

New therapeutic target against persistent viral infections

January 11, 2017
Life is a question of balance, and the body is no exception. Expression levels of certain proteins can affect the immune system's ability to neutralize a virus. Type I interferons (IFN-I) are cytokines that were previously ...

Hepatitis C virus: How viral proteins interact in human cells

May 8, 2014
Scientists at the Helmholtz Zentrum München have for the first time decrypted the interaction network of hepatitis C virus proteins in living human cells. Their findings will contribute to a better understanding of the mechanisms ...

Immune 'traffic jam' from viral infection interferes with therapeutic antibodies

February 12, 2015
Several drugs now used to treat cancer and autoimmune diseases are actually repurposed tools derived from the immune system. One of the ways these "therapeutic antibodies" work is to grab onto malignant or inflammatory cells ...

Scientists identify interferon beta as likely culprit in persistent viral infections

May 13, 2015
Interferon proteins are normally considered virus-fighters, but scientists at The Scripps Research Institute (TSRI) have found evidence that one of them, interferon beta (IFNβ), has an immune-suppressing effect that can ...

Study finds interferon, one of the body's proteins, induces persistent viral infection

April 11, 2013
Scientists at The Scripps Research Institute (TSRI) have made a counterintuitive finding that may lead to new ways to clear persistent infection that is the hallmark of such diseases as AIDS, hepatitis B and hepatitis C.

Recommended for you

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Zika virus damages placenta, which may explain malformed babies

January 18, 2018
Though the Zika virus is widely known for a recent outbreak that caused children to be born with microencephaly, or having a small head, and other malformations, scientists have struggled to explain how the virus affects ...

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018
Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations ...

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.