{"doi":"10.1101/2023.06.21.545948","title":"Divergent Outcomes Of Myeloid Cell Infection By Gammaherpesvirus 68 Reveal Stepwise Regulation By Host And Viral Factors","abstract":"Summary The gammaherpesviruses establish a lifelong infection, with the cellular outcome of infection intimately regulated by cell type. Though myeloid cells are an early infection target, infection results in widely divergent outcomes without a clear explanation. Here we use murine gammaherpesvirus 68 to demonstrate that macrophages are readily infectable, resulting in three divergent infection outcomes dictated by viral and host factors. Infection in vivo and in a cell culture model results in a high frequency of viable cells characterized by restricted viral transcription and unexpected transcription of the ORF75 locus, with rare cells initiating but failing to complete lytic replication. In contrast, infection with a high viral dose triggers abortive infection and cell death. Restricted infection can be fully converted to productive lytic replication by pre-treatment with the host cytokine IL-4. These studies demonstrate stepwise regulation of virus infection and identify virus and host factors that dictate divergent outcomes in a single cell type. Highlights MHV68 efficiently infects macrophages Infection results in three divergent outcomes regulated by discrete inputs Macrophages limit lytic replication at two distinct stages Macrophages are capable of lytic replication, promoted by the host cytokine IL-4 and viral genes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392455,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1166005,"name":"Kyra S. Noell","orcid":"0000-0003-3623-8822","position":1,"is_corresponding":false},{"id":1166006,"name":"Ashley Tseng","orcid":"0000-0002-3078-3718","position":2,"is_corresponding":false},{"id":336707,"name":"Rachael Kostelecky","orcid":"0000-0002-6529-3831","position":3,"is_corresponding":false},{"id":1166007,"name":"Elizabeth A. Alexander","orcid":"0000-0002-4859-4122","position":4,"is_corresponding":false},{"id":510108,"name":"Shirli Cohen","orcid":"0000-0002-0253-786X","position":5,"is_corresponding":false},{"id":1166008,"name":"Catalina Galvan","orcid":"0009-0009-3439-7644","position":6,"is_corresponding":false},{"id":1166009,"name":"Manaal Dalwadi","orcid":"0009-0005-3187-7803","position":7,"is_corresponding":false},{"id":1057527,"name":"B. Gómez","orcid":"0000-0002-3871-3773","position":8,"is_corresponding":false},{"id":585587,"name":"Eva M. Medina","orcid":"0000-0001-6899-0213","position":9,"is_corresponding":false},{"id":573921,"name":"Darby G. Oldenburg","orcid":"0000-0003-2090-7489","position":10,"is_corresponding":false},{"id":10973,"name":"Andrew Goodspeed","orcid":"0000-0001-7055-7128","position":11,"is_corresponding":false},{"id":28343,"name":"Eric T. Clambey","orcid":"0000-0002-7972-9544","position":12,"is_corresponding":false},{"id":564963,"name":"Linda F. van Dyk","orcid":"0000-0003-2662-5554","position":13,"is_corresponding":false},{"id":1166004,"name":"Gabrielle Vragel","orcid":"0000-0001-9167-3013","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":"37425871","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":[]}