Targeted cross-species transfer of HIV-1 to Felis catus cells to study virus evolution

• Applicant: Professor Dr. Carsten Münk
• Subject Area: Virology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 577149819

Cross-species transmissions of lentiviruses are rare and mostly seen between closely related mammal species. Only a few studies have addressed experimental virus evolution to study lentivirus cross-species transmissions. This project targets lentivirus evolution in a cross-species transmission model where some of the typical restriction factors are absent (TRIM5α, MX2) or counteracted (APOBEC3, SERINC5). Our hypothesis is that successful cross-species lentiviral transmissions depend on some level of virus pre-adaptation to dependency and restriction factors or a reduced expression of cellular antiviral factors. In our experiments, we use feline cell systems that naturally lack a TRIM5alpha restriction and escape the APOBEC3 restriction by expressing the FIV vif gene in HIV-1. Since such an approach would not be enough for an HIV-1 infection, we had to solve the ENV receptor infection block. We generated a full-length HIV-1 that uses a CD4-independent ENV, allowing it to infect feline cells without requiring a human CD4 protein. To understand lentiviral genetic adaptation in spreading replication in a new species, this project has three main goals: I) To observe how VIF proteins can adapt to new APOBEC3 restriction factors; II) to understand the genetic stability and evolutionary changes of CD4-independent envelope proteins; and III) to identify novel HIV-1 restriction factors and viral strategies to escape or counteract. Since HIV-1 adapted for human cells, the chance to identify novel antiviral pathways for HIV-1 in non-human cells is likely high. The goal here is to identify a new replication roadblock for HIV-1 and viral adaptation.

• DFG Programme: Research Grants