In-vivo-tracking, immune control and autoimmunity in genetic models of murine endogenous retrovirus reactivation

• Applicant: Dr. Philipp Yu
• Subject Area: Immunology ; Virology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258301698

HIV is the most infamous new emerging infectious disease in the last decades, still awaiting more effective treatment or successful vaccination. But retroviruses have posed a constant threat to mammals during evolution, culminating in invasion of the human and mouse genome, by so-called endogenous retroviruses (ERVs). Although their functionality as infectious retroviruses is still debated in humans, certain mouse strains can express ERVs, similar to murine leukemia virus (MuLV) and succumb to retrovirus induced disease. Recently, immunologists have demonstrated that both the impairment of adaptive (B cell mediated antibody production) or innate immune recognition (nucleic-acid-sensing TLRs -3,-7 and -9) results in uncontrolled ERV mediated retroviral viremia in murine model systems. However, the complexity of the immune response and potential interactions with a variety of cell intrinsic anti-retroviral mechanism warrant new models deciphering the basics of retroviral expression and immune control. Here, we propose the generation of tagged MuLV, which express fluorescent- or luciferase markers, that allow the in vivo detection of infectious retroviruses or the resurrection of experimentally introduced germline encoded ERVs. These models, in conjunction with the cellular and molecular analysis of ERV recognition and inhibition by innate and adaptive immunity, in particular the B cell response, might allow a better understanding of the biology of retroviral immune interactions in general. Finally, we will try to generate a genetic model, which addresses a mechanism how retroviruses could break self-tolerance and induce autoimmunity in vivo.

• DFG Programme: Research Grants