{"doi":"10.3390/v13040611","title":"FIB-SEM as a Volume Electron Microscopy Approach to Study Cellular Architectures in SARS-CoV-2 and Other Viral Infections: A Practical Primer for a Virologist","abstract":"The visualization of cellular ultrastructure over a wide range of volumes is becoming possible by increasingly powerful techniques grouped under the rubric \"volume electron microscopy\" or volume EM (vEM). Focused ion beam scanning electron microscopy (FIB-SEM) occupies a \"Goldilocks zone\" in vEM: iterative and automated cycles of milling and imaging allow the interrogation of microns-thick specimens in 3-D at resolutions of tens of nanometers or less. This bestows on FIB-SEM the unique ability to aid the accurate and precise study of architectures of virus-cell interactions. Here we give the virologist or cell biologist a primer on FIB-SEM imaging in the context of vEM and discuss practical aspects of a room temperature FIB-SEM experiment. In an in vitro study of SARS-CoV-2 infection, we show that accurate quantitation of viral densities and surface curvatures enabled by FIB-SEM imaging reveals SARS-CoV-2 viruses preferentially located at areas of plasma membrane that have positive mean curvatures.","journal":"Viruses","year":2021,"id":162118,"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":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562013,"name":"Ryan Conrad","orcid":"0000-0002-3057-9418","position":1,"is_corresponding":false},{"id":678360,"name":"Patrick Friday","orcid":"0000-0002-8214-4344","position":2,"is_corresponding":false},{"id":678361,"name":"Ella Fitzgerald","orcid":"0009-0004-6770-5985","position":3,"is_corresponding":false},{"id":678362,"name":"Taeeun Kim","orcid":"0000-0002-2075-4497","position":4,"is_corresponding":false},{"id":390601,"name":"John G. Bernbaum","orcid":"0000-0002-1529-8191","position":5,"is_corresponding":false},{"id":679342,"name":"Heather Berensmann","orcid":null,"position":6,"is_corresponding":false},{"id":521168,"name":"Adam Harned","orcid":"0000-0001-7771-5395","position":7,"is_corresponding":false},{"id":219831,"name":"Kunio Nagashima","orcid":null,"position":8,"is_corresponding":false},{"id":521170,"name":"Kedar Narayan","orcid":"0000-0001-7982-6494","position":9,"is_corresponding":false},{"id":571524,"name":"Valentina Baena","orcid":"0000-0002-6429-439X","position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":null,"created_at":"2026-07-18T23:45:00.600065Z","pmid":"33918371","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":[]}