{"doi":"10.1073/pnas.1921315117","title":"Necroptosis-based CRISPR knockout screen reveals Neuropilin-1 as a critical host factor for early stages of murine cytomegalovirus infection","abstract":"Herpesviruses are ubiquitous human pathogens that cause a wide range of health complications. Currently, there is an incomplete understanding of cellular factors that contribute to herpesvirus infection. Here, we report an antiviral necroptosis-based genetic screen to identify novel host cell factors required for infection with the β-herpesvirus murine cytomegalovirus (MCMV). Our genome-wide CRISPR-based screen harnessed the capacity of herpesvirus mutants that trigger antiviral necroptotic cell death upon early viral gene expression. Vascular endothelial growth factor (VEGF) and semaphorin-binding receptor Neuropilin-1 (Nrp-1) emerge as crucial determinants of MCMV infection. We find that elimination of Nrp-1 impairs early viral gene expression and reduces infection rates in endothelial cells, fibroblasts, and macrophages. Furthermore, preincubation of virus with soluble Nrp-1 dramatically inhibits infection by reducing virus attachment. Thus, Nrp-1 is a key determinant of the initial phase of MCMV infection.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":98625,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"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":486440,"name":"Hongyan Guo","orcid":"0000-0002-6286-1741","position":1,"is_corresponding":false},{"id":486441,"name":"Amanda Fisher","orcid":"0000-0002-2634-144X","position":2,"is_corresponding":false},{"id":486442,"name":"Jonathan Diep","orcid":"0000-0003-3876-2126","position":3,"is_corresponding":false},{"id":263243,"name":"Zhao Lai","orcid":"0000-0002-3543-5376","position":4,"is_corresponding":false},{"id":389888,"name":"Yidong Chen","orcid":"0000-0002-3154-6511","position":5,"is_corresponding":false},{"id":225736,"name":"Jason W. Upton","orcid":"0000-0002-4218-4026","position":6,"is_corresponding":false},{"id":227957,"name":"Jan E. Carette","orcid":"0000-0002-5187-8070","position":7,"is_corresponding":false},{"id":288423,"name":"Edward S. Mocarski","orcid":"0000-0002-8362-9490","position":8,"is_corresponding":false},{"id":225733,"name":"William J. Kaiser","orcid":"0000-0003-2479-133X","position":9,"is_corresponding":false},{"id":486439,"name":"Rebecca Lane","orcid":"0000-0002-5233-5422","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T22:36:58.511143Z","pmid":"32747526","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":[]}