Projects Computational Virology
Deep exploration of the virosphere for novel viruses in humans and other eukaryotes
We have established high performance computing-based workflows that allow us to efficiently and sensitively screen unprocessed NGS data from the Sequence Read Archive (SRA) for the presence of viruses that may have been sequenced as a by-product of sequencing the host genome or transcriptome. We have a particular interest in the discovery of highly divergent novel viruses. We want to explore the human virome as a potential factor of infection susceptibility as well as a possible cause of other diseases including primary immunodeficiencies and cancer. We seek to study inter-individual differences in virome composition between diseased and healthy persons. Furthermore, we extend our virus discovery approach to viruses in animals and other eukaryotes, aiming for (i) the identification of mammalian species harboring unknown relatives of human pathogenic viruses, which may form the basis for establishing new animal infection models, and (ii) the comprehensive description of virus-host co-evolution of RNA viruses across eukaryotes.
Funding: EXC 2155: RESIST, KA1-Co-02 CoViPa
Publications
Pandemic preparedness: assessing spill-over risk of RNA viruses
A major goal of our Helmholtz-funded project in the CoViPa consortium is to help increasing pandemic preparedness by means of computational high-throughput virus discovery and evolutionary analyses to identify both RNA viruses with high risk of spillover into the human population and potential animal host reservoirs. We utilize >149,000 RNA virus sequences discovered from our SRA screen of >500,000 eukaryotic transcriptome projects to study virus-host co-evolution and to identify viruses with broad host ranges that we hypothesize to having the highest likelihood for spillover. Moreover, we apply computational approaches to advance the functional characterization of the proteome of corona- and other nidoviruses in order to identify possible unknown pathogenicity factors of these viruses. In the mid-term, we plan to experimentally characterize potentially novel viral pathogenicity factors predicted by the bioinformatics analysis via expressing testing and functional phenotyping. to uncover for instance inhibitors of interferone signaling in collaboration with other RESIST and CoViPa members.
Funding: KA1-Co-02 CoViPa
Publications
Genetic determinants of severe RSV infection in infants
In close collaboration with Prof. Gesine Hansen (MHH) and Prof. Thomas Pietschmann (Twincore) we want to understand how the numerous changes in the human genome and their highly complex interplay can influence the severity of infections with the respiratory syncytial virus (RSV) among infants. Are there specific genetic variants that occur frequently in patients with a severe course of infection? Are very rare changes involved that differ from patient to patient but which influence the same cellular processes? In order to answer these and other questions, our collaborators have sequenced the exomes of about 175 young children with severe course of disease and a comparable number of controls with mild course of RSV infection. We apply bioinformatics and genetic association analyses to identify likely
Funding: EXC 2155: RESIST
Deep exploration of the virosphere for novel viruses in humans and other eukaryotes
Chong LC, Lauber C (2023) Viroid-like RNA-dependent RNA polymerase-encoding ambiviruses are abundant in complex fungi. Front Microbiol. 14:1144003. doi: 10.3389/fmicb.2023.1144003
Lauber C, Seitz S (2022) Opportunities and Challenges of Data-Driven Virus Discovery. Biomolecules 12(8):1073. doi: 10.3390/biom12081073.
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020) The Species Severe Acute Respiratory Syndrome-Related Coronavirus: Classifying 2019-nCoV and Naming It SARS-CoV-2. Nat Microbiol 5(4):536-544.
Lauber C*, Seitz S*, Mattei S, Suh A, Beck J, Herstein J, Borold J, Salzburger W, Kaderali L, Briggs JAG, Bartenschlager R (2017) Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses. Cell Host Microbe 22(3): 387-399 e386. * equal contribution
Pandemic preparedness: assessing spill-over risk of RNA viruses
Lauber C, Seifert M, Bartenschlager R, Seitz S (2019) Discovery of highly divergent lineages of plant-associated astro-like viruses sheds light on the emergence of potyviruses. Virus Res 260: 38-48.
Lauber C*, Seitz S*, Mattei S, Suh A, Beck J, Herstein J, Borold J, Salzburger W, Kaderali L, Briggs JAG, Bartenschlager R (2017) Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses. Cell Host Microbe 22(3): 387-399 e386. * equal contribution
van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, Osterhaus AD, Haagmans BL, Gorbalenya AE, Snijder EJ, Fouchier RA (2012) Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio 3(6).
Nga PT*, Parquet Mdel C*, Lauber C*, Parida M, Nabeshima T, Yu F, Thuy NT, Inoue S, Ito T, Okamoto K, Ichinose A, Snijder EJ, Morita K, Gorbalenya AE (2011) Discovery of the first insect nidovirus, a missing evolutionary link in the emergence of the largest RNA virus genomes. PLoS Pathog 7(9): e1002215. *equal contribution
Genetic determinants of severe RSV infection in infants
Haid S, Wetzke M, Todt D, Holwerda M, Dijkman R, Zillinger T, Jonigk D, Lange M, Kaderali L, Geffers R, Adhisantoso YG, Voges J, Ostermann J, Grethe C, Wiegmann B, Hansen G, Lauber C, Pietschmann T. TMEM259 alleles modulate respiratory syncytial virus infection and ER-stress-triggered apoptosis. Manuscript under review