{"doi":"10.1101/2020.10.26.355172","title":"Natural Cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling","abstract":"SUMMARY GPR15 is a G protein-coupled receptor proposed to play a role in mucosal immunity that also serves as entry cofactor for HIV and SIV. To discover novel endogenous GPR15 ligands, we screened a hemofiltrate-derived peptide library for inhibitors of GPR15-mediated SIV infection. Our approach identified a C-terminal fragment of Cystatin C (CysC95-146) that specifically inhibits GPR15-dependent HIV-1, HIV-2 and SIV infection. In contrast, GPR15L, the chemokine ligand of GPR15, failed to inhibit virus infection. We found that Cystatin C fragments preventing GPR15-mediated viral entry do not interfere with GPR15L signaling and are generated by proteases activated at sites of inflammation. The antiretroviral activity of CysC95-146 was confirmed in primary CD4+ T cells and is conserved in simian hosts of SIV infection. Thus, we identified a potent endogenous inhibitor of GPR15-mediated HIV and SIV infection that does not interfere with the physiological function of this G protein-coupled receptor.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124145,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":569292,"name":"Andrea Blötz","orcid":null,"position":1,"is_corresponding":false},{"id":568448,"name":"Armando Rodríguez","orcid":"0000-0001-5921-3770","position":2,"is_corresponding":false},{"id":568449,"name":"Solange Vidal","orcid":"0000-0003-0289-9569","position":3,"is_corresponding":false},{"id":569293,"name":"Nico Preising","orcid":null,"position":4,"is_corresponding":false},{"id":569294,"name":"Ludger Ständker","orcid":null,"position":5,"is_corresponding":false},{"id":172893,"name":"Sebastian Wiese","orcid":"0000-0001-5697-2608","position":6,"is_corresponding":false},{"id":386592,"name":"Christina M. Stürzel","orcid":null,"position":7,"is_corresponding":false},{"id":568450,"name":"Mirja Harms","orcid":"0000-0002-5460-5166","position":8,"is_corresponding":false},{"id":568451,"name":"Rüdiger Groß","orcid":"0000-0003-0355-7915","position":9,"is_corresponding":false},{"id":568452,"name":"Christoph Jung","orcid":"0000-0002-1422-4991","position":10,"is_corresponding":false},{"id":569295,"name":"Miriam Kiene","orcid":null,"position":11,"is_corresponding":false},{"id":91120,"name":"Beatrice H. Hahn","orcid":"0000-0002-9400-9887","position":12,"is_corresponding":false},{"id":568453,"name":"Timo Jacob","orcid":"0000-0001-7777-2306","position":13,"is_corresponding":false},{"id":241083,"name":"Stefan Pöhlmann","orcid":"0000-0001-6086-9136","position":14,"is_corresponding":false},{"id":569296,"name":"Wolf‐Georg Forssmann","orcid":null,"position":15,"is_corresponding":false},{"id":568454,"name":"Jan Münch","orcid":"0000-0001-7316-7141","position":16,"is_corresponding":false},{"id":468046,"name":"Konstantin M. J. Sparrer","orcid":"0000-0002-8682-1779","position":17,"is_corresponding":false},{"id":568455,"name":"Klaus Seuwen","orcid":"0000-0002-6847-6676","position":18,"is_corresponding":false},{"id":350334,"name":"Frank Kirchhoff","orcid":"0000-0002-7052-2360","position":19,"is_corresponding":false},{"id":568447,"name":"Manuel Hayn","orcid":"0000-0001-5908-3099","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}