Cellular restriction factors and innate sensing of human and non-human endogenous retroviruses

• Applicants: Professor Dr. Norbert Bannert; Oya Cingöz, Ph.D.
• Subject Area: Virology
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318216570

Vertebrates developed countermeasures for protection from exogenous retroviruses and excessive proliferation of endogenous retroviruses. Along these lines we showed that infection of HERV-K(HML-2), a human endogenous retrovirus able to form viral particles, is significantly inhibited in several cell lines. This inhibition can be attenuated by decoy cores of the same virus arguing for the presence of a cellular restriction factor. Results obtained in the first phase of the programme indicate that the elusive factor(s) acts at a post RT step. The first main goal of the second phase will therefore be the further characterization of the post RT block and the identification of the cellular restriction factor(s). A second aim is based on our recent observation that HERV-K(HML-2) particle production is strongly inhibited by the interferon inducible protein 16 (IFI16). We plan to examine various aspects of this restriction including the IFI16 effect on transcription and epigenetic modifications at the DNA level. This study will be extended to other betaretroviruses and additional members of the PYHIN-family proteins. Finally, based on our findings that the accessory protein Vpx from some SIV and HIV lineages sensitizes infected cells to innate immune signaling, we will determine whether the same process also applies to endogenous and exogenous members of the betaretrovirus genus. We will identify the viral and cellular determinants of the IFN signaling triggered by infection in primary cells, and use these results to elucidate the mechanism of how different retroviruses are able to escape or inhibit innate immune sensing in host cells.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1923: Innate Sensing and Restriction of Retroviruses