Genomics of Retroviral Infection - Dr. Dr. Ulrike Lange

Human Immunodeficiency Virus (HIV) is a contemporary retrovirus that replicates through integration of proviral DNA into the genome of infected cells. This remarkable viral life cycle brings about several intriguing features. Integrated proviral sequences can be transcriptionally repressed, resulting in a latently infected reservoir that is hampering current efforts to eradicate HIV once infection has occurred. Furthermore, chronically HIV-infected patients accumulate a large number of defective proviral sequences within the genomes of HIV target cell. Very little is known to date about the impact of these sequences on host cell biology.

The junior research subunit Genomics of Retroviral Infection investigates how retroviruses, like HIV, impact on the biology of target genomes and vice versa. We are interested in the molecular mechanisms that determine selection of genomic HIV integration sites as well as HIV latency establishment and maintenance in chronic infection. Particular emphasis also lies on analysis of broader changes in genome biology. To explore these, we study the regulation of human endogenous retroviral (HERV) elements in the context of HIV infection. These elements are derived from ancient retroviral infection events, which have left our genome covered with thousands of viral-derived sequences. The overall aim is to understand how integration of retroviral DNA modifies host genomic activity and thus impacts on host cell physiology and contributes to pathology.

In order to approach these questions, we employ a range of experimental techniques, focusing in particular on analysis of local and genome-wide epigenetic and transcriptional states and making use of site-specific targeting technologies to generate suitable cellular models for functional analyses. Our work is also based on investigation of immune cell subsets from patient cohorts and healthy individuals, as well as bioinformatic integrative analyses.