Towards a rabbit model of HIV infection

• Applicant: Privatdozentin Dr. Hanna-Mari Baldauf
• Subject Area: Virology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 438517132

An immunocompetent, permissive small animal model facilitates studies on HIV pathogenesis and testing of HIV vaccine candidates. A first step towards the development of a HIV animal model has been the identification and surmounting of species-specific barriers that HIVencounters along its replication cycle in cells from small animals. These barriers are either due to missing or non-compatible cellular co-factors, which HIV requires for efficient replication, or due to the presence of restriction factors, which block HIV replication at different steps of its life cycle. We have recently shown that primary rabbit cells display a high natural permissivity to HIV-1 infection. HIV Encounters three replication barriers in this species – the first two are at the Level of virus entry and reverse transcription and the third barrier limits HIV infectivity in rabbit macrophages. Our central hypothesis is that rabbits are fully susceptible after overcoming the three barriers to HIV replication. The goal of this proposal is study these barriers in more detail and to overcome them in rabbit cells. Overexpressing the human HIV receptor complex and knocking out rabbit TRIM5 should already provide full-round replication in rabbit cell lines. Furthermore, we will re-evaluate the role of the receptor complex, consisting of CD4/CCR5 or CD4/CXCR4, during HIV entry into rabbit cells. Identifying the nature of the third replication barrier in primary rabbit macrophages will further advance our efforts to generate a permissive rabbit model for HIV infection.

• DFG Programme: Research Grants