SPP 1923:  Innate Sensing and Restriction of Retroviruses

• Subject Area: Medicine ; Biology
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 273898015

Retroviruses comprise a diverse group of exogenous and endogenous viruses defined by their unique replication strategy to reverse-transcribe their RNA genome into a complementary DNA. Millions of years of coevolution with their mammalian hosts gave rise to highly pathogenic as well as apathogenic members of this family of viruses and to species-specific differences in their pathologic potential. Evidence is emerging that cell-type specific cell-autonomous components of the innate immune system, including specialized pattern recognition receptors and broadly active antiviral restriction factors, represent key determinants of the fundamentally different outcomes of retroviral infections. However, the specific host cell machineries involved in recognizing retroviral infection, viral evasion strategies thereof, and their relative contribution to retroviral pathogenesis in specific target cells and organs remain to be defined. Priority Program SPP1923 (Innate sensing of restriction of retroviruses) thus aims at the identification of the full molecular sensing and restriction machinery involved in cell-autonomous immunity against retroviruses, its regulation, virus-encoded countermeasures, and pathophysiological consequences. During the first funding period of SPP1923, a strong collaborative research and training network of retrovirologists and innate immunologists was developed that defined novel important molecular mechanisms and cell-type or species-specific principles of retroviral sensing and restriction of retroviruses. Work during the second funding period will build on these findings and the interdisciplinary network established with the goal to gain detailed molecular and physiological understanding of these processes. Central funds are requested for an SPP office that assists the SPP coordinator in managing SPP activities and for networking activities such as SPP internal meetings, workshops, exchange of co-workers and an international SPP conference.

• DFG Programme: Priority Programmes

Projects

• Antagonism of Host Cell Restriction and Sensing by HIV-1 Nef (Applicant Fackler, Ph.D., Oliver T. )
• Capsid-dependent innate sensing and restriction or retroviral replication complexes (Applicant Kräusslich, Hans-Georg )
• Cellular and Viral Determinants of Innate HIV Recognition in Macrophages (Applicants Hornung, Veit ;  Keppler, Oliver Till )
• Cellular restriction factors and innate sensing of human and non-human endogenous retroviruses (Applicants Bannert, Norbert ;  Cingöz, Ph.D., Oya )
• Consequences of CTL-mediated immune pressure for HIV-1 capsid stability and innate sensing (Applicant Altfeld, Marcus )
• Coordination Funds (Applicant Fackler, Ph.D., Oliver T. )
• Counteraction of innate sensing and retroviral restriction by patient-derived HIV-1 Vpr. (Applicant Schindler, Michael )
• Host cell peptidylprolyl cis-trans isomerases as immune modulators of HIV-1 infection (Applicant Kräusslich, Hans-Georg )
• Inhibition of type Interferon production by murine leukemia retrovirus (MuLV) (Applicant Bauer, Stefan )
• Interferon-induced alteration of cellular factors affecting HIV alternative splicing, nuclear mRNA export and LTR transcription (Applicant Widera, Marek )
• Investigation of cellular mechanism of PQBP1-dependant innate signaling of HIV-1 (Applicant König, Renate )
• Investigation of Innate Immune Responses against HIV with Camelid Nanobodies (Applicants Latz, Eicke ;  Schmidt, Florian Ingo )
• Mechanisms of inflammasome activation and pyroptosis induction by HIV (Applicant Latz, Eicke )
• Mechanisms of innate immune system sensing and evasion during foamy virus infections (Applicant Lindemann, Dirk )
• Modulation of cell-intrinsic innate immunity to improve “shock-and-kill” strategies of HIV-1 cure (Applicant Goffinet, Christine )
• Nanodiamonds as sensitive sensors to study tetherin structure and dynamics (Applicants Jelezko, Fedor ;  Kirchhoff, Frank ;  Weil, Tanja )
• Regulation of the induction of IFNα subtypes during HIV infection (Applicants Dittmer, Ulf ;  Sitek, Barbara ;  Sutter, Kathrin )
• Restriction of endogenous retroviruses by chromatin regulators (Applicant Schotta, Gunnar )
• Role of PYHIN proteins in retroviral restriction, spread and latency (Applicant Kirchhoff, Frank )
• Role of Shiftless in HIV infection: Antiviral mechanism and contribution to innate immune responses (Applicants Pöhlmann, Stefan ;  Rodnina, Marina V. )
• The role of bystander cell autophagy in HIV-1 infection (Applicant Sparrer, Konstantin )
• The role of TREX1 for innate sensing human endogenous retroviruses (Applicants Fackler, Ph.D., Oliver T. ;  Ruggieri, Ph.D., Alessia )
• Transcriptional regulation of innate immunity – interplay of exogenous and endogenous retroviruses (Applicant Sauter, Daniel )
• USP18 modulates the sensing of HIV-1 (Applicant Münk, Carsten )

• Spokesperson: Professor Oliver T. Fackler, Ph.D.