Projects Computational Virology

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? Or are rather 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 more than 100 young children with severe course of disease, and we apply bioinformatics and genetic association analyses to identify likely causal variants in immunity-related genes. The effect of genetic variants of these candidate genes will then be validated experimentally by our collaborators.
Funding: EXC 2155: RESIST
The human virome in health and disease
In this project we want to explore the human virome as a potential factor of infection susceptibility. We seek to determine the number and diversity of viruses associated with humans, as comprehensively and as tissue-specific as possible. To do so, we analyze high-throughput sequencing data from potential hosts for the presence of viral genetic information using sensitive bioinformatics approaches. The basic premise here is that the viral genome will be sequenced along the host genome or transcriptome if the individual was infected with that virus at the time of sampling. To discover such cases, we develop computational workflows for sensitive homology search and targeted genome assembly from NGS data and we make use of high-performance computing for parallel execution of these tools. Although we look broadly for all types of viruses, we are particularly interested in viruses with DNA genomes, for instance herpes-, polyma- and anelloviruses as well as CRESS DNA viruses, which may cause persistent infections in humans. We also aim at exploring potential associations of the giant Nucleo-cytoplasmic large DNA viruses (NCLDVs) with disease in humans.
The vertebrate RNA virome
In addition to the study of the human virome, we will apply our workflows to animal samples with the aim to discover unknown relatives of major human pathogens. We will focus in this project on RNA viruses, in particular on those that may cause chronic infections in humans. For example, we will search for new viruses related to the hepadna-, hepaci-, hepe- and deltaviruses causing liver disease in humans. Although we are primarily interested in mammalian viruses, we will also look for new viruses of other vertebrate species, since both could give valuable insights into the evolution of their relatives infecting humans. Suitable candidate viruses will be characterized experimentally by our collaborators. Ultimately, we aim at establishing the basis for animal infection models.
Publications
The human virome in health and disease
Lauber C*, Seitz S*, Mattei S, Suh A, Beck J, Herstein J, Börold J, Salzburger W, Kaderali L, Briggs JAG, Bartenschlager R. Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses. Cell Host Microbe. 2017 Sep 13;22(3):387-399
van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, Osterhaus AD, Haagmans BL, Gorbalenya AE, Snijder EJ, Fouchier RA. Genomic Characterization of a Newly Discovered Coronavirus Associated With Acute Respiratory Distress Syndrome in Humans. mBio. 2012 Nov 20;3(6):e00473-12
van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. Discovery of a New Human Polyomavirus Associated With Trichodysplasia Spinulosa in an Immunocompromized Patient. PLoS Pathog. 2010 Jul 29;6(7):e1001024
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The Species Severe Acute Respiratory Syndrome-Related Coronavirus: Classifying 2019-nCoV and Naming It SARS-CoV-2. Nat Microbiol. 2020 Apr;5(4):536-544
*equal contribution
The RNA virome in vertebrates
Lauber C, Seifert M, Bartenschlager R, Seitz S. Discovery of Highly Divergent Lineages of Plant-Associated Astro-Like Viruses Sheds Light on the Emergence of Potyviruses. Virus Res. 2019 Jan 15;260:38-48
Lauber C*, Seitz S*, Mattei S, Suh A, Beck J, Herstein J, Börold J, Salzburger W, Kaderali L, Briggs JAG, Bartenschlager R. Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses. Cell Host Microbe. 2017 Sep 13;22(3):387-399
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. Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes. PLoS Pathog. 2011 Sep;7(9):e1002215
*equal contribution