{"doi":"10.1002/jmv.29818","title":"GBP1, an interferon‐inducible GTPase, inhibits Hantaan viral entry by restricting clathrin‐mediated endocytosis","abstract":"Hantaviruses belong to the Hantaviridae family of the Bunyavirales order1 that can cause severe and sometimes fatal viral hemorrhagic diseases in humans.2 They are found throughout Eurasia and the Americas and are primarily carried by rodents (as well as some other animals, such as moles, shrews, bats, reptiles, and fish, with a species-level host specificity for each virus3). Human infection usually results from exposure to aerosolized excrement of infected rodents,1, 2 though there have been reports of human-to-human transmission for Andes virus.4, 5 Infection with Old-World (OW) hantaviruses can lead to hemorrhagic fever with renal syndrome (HFRS) with mortality rates below 1% for most OW hantaviruses except for the 5%–15% noted for infections with Dobrava virus or possibly Hantaan virus.6-9 New-World (NW) hantaviruses are more often associated with hantavirus cardiopulmonary syndrome (HCPS) and have higher mortality rates of 10%–45%.6, 10 Symptoms of HRFS include systemic vascular inflammation, thrombocytopenia, respiratory symptoms, and eventual kidney failure and hemorrhage that can result in death.6, 7, 11, 12 There are currently no preventative vaccines or targeted treatments available for hantavirus infection. Hantaan virus (HTNV) is an OW hantavirus that was first discovered in 1978 by surveilling wild striped-field mice (Apodemus agrarius) in endemic areas in North and South Korea.13, 14 It has since been identified throughout northeast Asia15 and is the main causative agent of HRFS in China.16 HTNV is an interferon-inducible virus in vitro17-19 and in vivo,19 highlighting the importance of identifying interferon-stimulated genes (ISGs) induced by HTNV infection to understand its life cycle and to identify potential antiviral therapeutic targets. A recent RNA sequencing study of HTNV-infected human endothelial cells identified interferon-inducible guanylate binding protein 1 (GBP1) as one such ISG, which was confirmed as an antiviral agent of HTNV infection by the observation of an increase in viral replication upon siRNA-mediated knockdown of GBP1.20 GBP1 has also been found to inhibit replication of several other viruses through its GTPase activity,21, 22 which has been found to be critical for interacting with cellular proteins such as STING23 and actin.24 To investigate the role of GBP1 in controlling HTNV infection, the authors of a recently accepted article in the Journal of Medical Virology, which has been selected as an editor's choice paper, utilized an in vitro approach to observe its effect on viral replication and cellular protein expressions.25 They reiterated previous finding that GBP1 was expressed during HTNV infection and expanded on this finding to show that GBP1 inhibited HTNV infection (as demonstrated by GPB1 overexpression and knockout assays). They furthermore found that while GBP1 expression was interferon dependent, the gene itself did not amplify interferon signaling and was able to inhibit HTNV in interferon-deficient cells. Given that different methods were used to inhibit interferon (IFN) signaling to observe effects on GBP1 expression (e.g., using ruxolitinib or RUX treatment to inhibit JAK1/2 signaling26) and the fact that GBP1 overexpression did not affect RIG-I/MDA5-elicited IFN signaling but inhibited HTNV infection in STAT1 knock out cells, it is possible that some of these findings may be reflective of the cellular context or assaying conditions (e.g., whether RUX treatment to inhibit JAK1/2 signaling could have an off-target effect, etc.). The authors then focused their attention on the timing of GPB1 inhibition of HTNV. They found that GBP1 was most effective at inhibiting the early stages of the viral life cycle, with GBP1 overexpression decreasing viral RNA synthesis at the earliest detectable timepoint of 24 h postinfection. Furthermore, GBP1 inhibitory effect was eliminated by overexpressing it at 2 h after viral infection and by including a neutralizing antibody in cell cul","journal":"Journal of Medical Virology","year":2024,"id":480726,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":233282,"name":"Hinh Ly","orcid":"0000-0001-8271-2033","position":1,"is_corresponding":false},{"id":233278,"name":"Morgan Brisse","orcid":"0000-0002-7040-4495","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:07:02.142014Z","pmid":"39011797","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":[]}