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

Scientists a step closer to predicting epidemics

July 13, 2018
Ecologists at the University of Georgia have taken an important step in their efforts to develop an early warning system for infectious disease outbreaks.

Researchers identify target for novel malaria vaccine

July 13, 2018
A Yale-led team of researchers have created a vaccine that protects against malaria infection in mouse models, paving the way for the development of a human vaccine that works by targeting the specific protein that parasites ...

Higher income and being married protect older people from broken bones

July 13, 2018
Research led by scientists from the Medical Research Council Lifecourse Epidemiology Unit (MRC LEU) at the University of Southampton has shown that a higher income and being married reduces the risk of experiencing a broken ...

Gammaherpesviruses linked to tumors in macaques with simian immunodeficiency virus

July 12, 2018
Viruses known as gammaherpesviruses may raise the risk of cancer in macaques infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV), according to new research published by Vickie Marshall ...

Scientists find protein exploited by virus ravaging West Africa

July 12, 2018
A research team from several institutions being led by the University of California San Diego has deciphered a key component behind a rising epidemic of pathogens that the World Health Organization (WHO) recently added to ...

How a Mediterranean diet could reduce osteoporosis

July 11, 2018
Eating a Mediterranean-type diet could reduce bone loss in people with osteoporosis—according to new research from the University of East Anglia.

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.