Lymphocytic choriomeningitis virus (LCMV) served as an indispensable model system for chronic viral infections over the last 80 years; two Nobel prizes were awarded for its exploration. However, the molecular interactions during the life cycle of the virus were hitherto poorly understood. In a new study, published in PLOS Pathogens, CeMM scientists revealed the comprehensive set of cellular proteins that physically interact with the LCMV polymerase – a key enzyme for the development of a chronic infection. 

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

With their latest study published in PLOS Pathogens (DOI 10.1371/journal.ppat.1006758) the team of Andreas Bergthaler, Principal Investigator at CeMM, 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 virus and for chronic infection. By mapping them in the human proteome, they revealed various viral strategies and potential targets for future antiviral therapeutics.

In order to perform the study, the researchers – with CeMM PhD student Kseniya Khamina as first author – developed a novel approach to tag viral proteins. Therewith, 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 a mapping of 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.

Publication:

Kseniya Khamina, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, Anannya Bhattacharya, Peter Májek, Alexey Stukalov, Roberto Sacco, Leo C. James, Daniel D. Pinschewer, Keiryn L. Bennett, Jörg Menche, and Andreas Bergthaler. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLOS Pathogens, December 20, 2017. DOI: 10.1371/journal.ppat.1006758

Funding:

The study was funded by the City of Vienna and the Austrian Academy of Sciences.