{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:38:00Z","timestamp":1760060280148,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Medical Research Council (SAMRC)","award":["HDID5149\/KR\/202","57009"],"award-info":[{"award-number":["HDID5149\/KR\/202","57009"]}]},{"name":"Mangosuthu University of Technology (MUT)","award":["HDID5149\/KR\/202","57009"],"award-info":[{"award-number":["HDID5149\/KR\/202","57009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background and Aim: The immunological interactions between soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2), particularly in the context of co-infection, are poorly understood. Next-generation sequencing (NGS) offers a powerful approach to explore these complex immune responses and uncover potential therapeutic targets. This study leveraged NGS and bioinformatic tools to investigate transcriptional changes and immunological pathways in female genital tract (FGT) tissues of BALB\/c mice acutely infected with Nippostrongylus brasiliensis (Nb), HSV-2, or co-infected. Methods: Total RNA was harvested from FGT tissues of BALB\/c mice infected with Nb, HSV-2, co-infected with both pathogens, and uninfected controls. Differentially expressed genes (DEGs) were identified by comparing uninfected versus infected FGT tissues in R using edgeR and limma packages. Immune-related genes were identified by intersecting DEGs in each group-wise comparison with immune function gene sets derived from the Mouse Genome Informatics (MGI) database. Functional and pathway enrichment analyses were performed with g: Profiler and protein\u2013protein interaction networks were built using the STRING database and visualized with Cytoscape. Key hub genes and significant gene modules were identified using the Cytoscape plugins CytoHubba and MCODE, followed by further functional analysis of these modules. Results: NGS analysis revealed distinct gene expression profiles in response to single infection with Nb or HSV-2, with both showing significant differences when uninfected controls were compared to infected FGT tissues at a 5% false discovery rate. Notably, there were no significant differences in gene expression profiles between uninfected and co-infected FGT tissues. In the comparison of uninfected versus Nb-infected FGT tissues, 368 DEGs were identified, with 356 genes upregulated and 12 downregulated. Several immune-related genes, such as Ptprc, Ccl11, Ccr2, and Cx3cr1, were significantly altered. Pathway analysis of DEGs, hub genes, and significant modules indicated modulation of immune and defense responses. Notably, Nb infection induced a robust Th2-dominant immune response in the FGT, with downregulation of pro-inflammatory genes. This likely reflects helminth-driven modulation that may impair protective Th1 responses and highlights the systemic impact of Nb on the FGT immunity. In the comparison of uninfected versus HSV-2-infected FGT tissues, 140 DEGs were identified, with 121 upregulated and 19 downregulated. Immune-related genes, including Ldlr, Camk1d, Lrp8 and Epg5, were notably altered. HSV-2 infection led to early and predominant downregulation of immune genes, consistent with viral immune evasion strategies. In addition, functional analysis revealed enrichment in cell cycle and sterol biosynthesis pathways, suggesting that HSV-2 modulates host metabolism to support viral replication while influencing immune responses. In co-infection, no significant transcriptional changes were observed, potentially reflecting immune antagonism where Nb-induced Th2 responses may suppress HSV-2-driven Th1 immune responses. Conclusions: This preliminary study offers insights into the gene expression responses in the FGT to acute single and co-infection with Nb and HSV-2. Together, these findings reveal distinct transcriptomic changes in the FGT following Nb and HSV-2 infection, with co-infection potentially leading to immune antagonism and transcriptional equilibrium. This highlights the complex interplay between helminth- and virus-induced immune modulation in shaping FGT immunity. By leveraging NGS, this study highlights important immune-related pathways and serves as a foundation for further investigations into the mechanistic roles of DEGs in immunity to these pathogens, with potential implications for developing novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/pathogens14080795","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:02:09Z","timestamp":1754910129000},"page":"795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Gene Expression Changes in Murine Female Genital Tract Tissues Following Single and Co-Infection with Nippostrongylus brasiliensis and Herpes Simplex Virus Type 2"],"prefix":"10.3390","volume":"14","author":[{"given":"Roxanne","family":"Pillay","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Applied and Health Sciences, Mangosuthu University of Technology, Umlazi, Durban 4031, South Africa"},{"name":"Department of Medical Microbiology, School of Laboratory Medicine & Medical Sciences, College of Health Sciences, Nelson R. Mandela School of Medicine Campus, University of KwaZulu-Natal, Durban 4001, South Africa"},{"name":"Division of Research Capacity Development, South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8905-5926","authenticated-orcid":false,"given":"Pragalathan","family":"Naidoo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, School of Laboratory Medicine & Medical Sciences, College of Health Sciences, Nelson R. Mandela School of Medicine Campus, University of KwaZulu-Natal, Durban 4001, South Africa"},{"name":"Division of Research Capacity Development, South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilungile L.","family":"Mkhize-Kwitshana","sequence":"additional","affiliation":[{"name":"Division of Research Capacity Development, South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa"},{"name":"Biomedical Sciences Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida Campus, Johannesburg 1710, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2471\/BLT.19.237149","article-title":"Herpes simplex virus: Global infection prevalence and incidence estimates, 2016","volume":"98","author":"James","year":"2020","journal-title":"Bull. World Health Organ."},{"key":"ref_2","unstructured":"World Health Organisation (2025, June 20). Soil-Transmitted Helminth Infections. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/soil-transmitted-helminth-infections."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hotez, P.J., and Kamath, A. (2009). Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden. PLoS Neglected Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000412"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chetty, A., Omondi, M.A., Butters, C., Smith, K.A., Katawa, G., Ritter, M., Layland, L., and Horsnell, W. (2020). Impact of Helminth Infections on Female Reproductive Health and Associated Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.577516"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nm.3103","article-title":"Rapid host immune response and viral dynamics in herpes simplex virus-2 infection","volume":"19","author":"Schiffer","year":"2013","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jri.2011.01.001","article-title":"Innate and adaptive immunity against herpes simplex virus type 2 in the genital mucosa","volume":"88","author":"Chan","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3390\/v6020371","article-title":"HSV-2 Vaccine: Current Status and Insight into Factors for Developing an Efficient Vaccine","volume":"6","author":"Zhu","year":"2014","journal-title":"Viruses"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"979","DOI":"10.3390\/v1030979","article-title":"Innate and adaptive immune responses to herpes simplex virus","volume":"1","author":"Chew","year":"2009","journal-title":"Viruses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.immuni.2017.11.015","article-title":"Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth Infection","volume":"47","author":"Harris","year":"2017","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.it.2018.06.002","article-title":"Helminth-Bacterial Interactions: Cause and Consequence","volume":"39","author":"Rapin","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1128\/CMR.05040-11","article-title":"Helminth infections and host immune regulation","volume":"25","author":"McSorley","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mkhize-Kwitshana, Z.L., Taylor, M., Jooste, P., Mabaso, M.L.H., and Walzl, G. (2011). The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa. BMC Infect. Dis., 11.","DOI":"10.1186\/1471-2334-11-273"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"910","DOI":"10.4102\/phcfm.v7i1.910","article-title":"Intestinal helminth infections amongst HIV-infected adults in Mthatha General Hospital, South Africa","volume":"7","author":"Adeleke","year":"2015","journal-title":"Afr. J. Prim. Health Care Fam. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/infdis\/jiv498","article-title":"Soil-Transmitted Helminth Infections Are Associated with an Increase in Human Papillomavirus Prevalence and a T-Helper Type 2 Cytokine Signature in Cervical Fluids","volume":"213","author":"Gravitt","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Holali Ameyapoh, A., Katawa, G., Ritter, M., Tchopba, C.N., Tchadi\u00e9, P.E., Arndts, K., Kamassa, H.E., Mazou, B., Amessoudji, O.M., and N\u2019djao, A. (2021). Hookworm Infections and Sociodemographic Factors Associated with Female Reproductive Tract Infections in Rural Areas of the Central Region of Togo. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.738894"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Omondi, M.A., Kamassa, E.H., Katawa, G., Tchopba, C.N., Vogelbusch, C., Parcina, M., Tchadi\u00e9, E.P., Amessoudji, O.M., Arndts, K., and Karou, S.D. (2022). Hookworm infection associates with a vaginal Type 1\/Type 2 immune signature and increased HPV load. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1009968"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.chom.2021.02.004","article-title":"Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection","volume":"29","author":"Chetty","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chin, C.-H., Chen, S.-H., Wu, H.-H., Ho, C.-W., Ko, M.-T., and Lin, C.-Y. (2014). cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_19","first-page":"12","article-title":"Animal model of Nippostrongylus brasiliensis and Heligmosomoides polygyrus","volume":"55","author":"Camberis","year":"2003","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shao, Q., Wu, F., Liu, T., Wang, W., Liu, T., Jin, X., Xu, L., Ma, Y., Huang, G., and Chen, Z. (2021). JieZe-1 Alleviates HSV-2 Infection-Induced Genital Herpes in Balb\/c Mice by Inhibiting Cell Apoptosis via Inducing Autophagy. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.775521"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Merle, N.S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V., and Roumenina, L.T. (2015). Complement System Part II: Role in Immunity. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00257"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1600-0897.2010.00842.x","article-title":"Sex hormone regulation of innate immunity in the female reproductive tract: The role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens","volume":"63","author":"Wira","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Agostinis, C., Mangogna, A., Bossi, F., Ricci, G., Kishore, U., and Bulla, R. (2019). Uterine Immunity and Microbiota: A Shifting Paradigm. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02387"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cytogfr.2022.05.002","article-title":"Chemokines and chemokine receptors: Insights from human disease and experimental models of helminthiasis","volume":"66","author":"Kraemer","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.113.007724","article-title":"International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors","volume":"66","author":"Bachelerie","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.pt.2016.05.004","article-title":"Eosinophils in Helminth Infection: Defenders and Dupes","volume":"32","author":"Huang","year":"2016","journal-title":"Trends Parasitol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5730","DOI":"10.4049\/jimmunol.168.11.5730","article-title":"CCR3 Is Required for Tissue Eosinophilia and Larval Cytotoxicity After Infection with Trichinella spiralis1","volume":"168","author":"Gurish","year":"2002","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1002\/eji.200535492","article-title":"The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection","volume":"36","author":"Dixon","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/S0002-9440(10)65394-1","article-title":"Effect of C-C Chemokine Receptor 2 (CCR2) Knockout on Type-2 (Schistosomal Antigen-Elicited) Pulmonary Granuloma Formation: Analysis of Cellular Recruitment and Cytokine Responses","volume":"154","author":"Warmington","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6280","DOI":"10.1128\/IAI.01609-05","article-title":"The Innate Immune Responses of Colonic Epithelial Cells to Trichuris muris Are Similar in Mouse Strains That Develop a Type 1 or Type 2 Adaptive Immune Response","volume":"74","author":"deSchoolmeester","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1172\/JCI127963","article-title":"Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development","volume":"129","author":"Ricciardi","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1046\/j.0141-9838.2001.00437.x","article-title":"Chemokine and cytokine expression in murine intestinal epithelium following Nippostrongylus brasiliensis infection","volume":"24","author":"Rosbottom","year":"2002","journal-title":"Parasite Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.4049\/jimmunol.170.9.4693","article-title":"Absence of CC Chemokine Ligand 2 Results in an Altered Th1\/Th2 Cytokine Balance and Failure to Expel Trichuris muris Infection1","volume":"170","author":"deSchoolmeester","year":"2003","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kim, S.Y., Barnes, M.A., Sureshchandra, S., Menicucci, A.R., Patel, J.J., Messaoudi, I., and Nair, M.G. (2022). CX3CR1-Expressing Myeloid Cells Regulate Host\u2013Helminth Interaction and Lung Inflammation. Adv. Biol., 6.","DOI":"10.1002\/adbi.202101078"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"632","DOI":"10.4049\/jimmunol.2300451","article-title":"Recruitment and Maintenance of CX3CR1+CD4+ T Cells during Helminth Infection","volume":"212","author":"Loredan","year":"2024","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.pt.2017.05.004","article-title":"Th2 and Th1 Responses: Clear and Hidden Sides of Immunity Against Intestinal Helminths","volume":"33","author":"Esteban","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1080\/21505594.2021.1982373","article-title":"Pathogenesis and virulence of herpes simplex virus","volume":"12","author":"Zhu","year":"2021","journal-title":"Virulence"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.4049\/jimmunol.1401538","article-title":"HSV-2 immediate-early protein US1 inhibits IFN-\u03b2 production by suppressing association of IRF-3 with IFN-\u03b2 promoter","volume":"194","author":"Zhang","year":"2015","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Guan, X., Zhang, M., Fu, M., Luo, S., and Hu, Q. (2019). Herpes simplex virus type 2 immediate early protein ICP27 inhibits IFN-\u03b2 production in mucosal epithelial cells by antagonizing IRF3 activation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00290"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.4049\/jimmunol.2000418","article-title":"Herpes simplex virus type 2 inhibits type I IFN signaling mediated by the novel E3 ubiquitin protein ligase activity of viral protein ICP22","volume":"205","author":"Zhang","year":"2020","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jri.2003.12.002","article-title":"T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice","volume":"61","author":"Milligan","year":"2004","journal-title":"J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1126\/science.1257530","article-title":"T cell memory. A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells","volume":"346","author":"Iijima","year":"2014","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/febs.13150","article-title":"BRCA1, a \u2018complex\u2019 protein involved in the maintenance of genomic stability","volume":"282","author":"Savage","year":"2015","journal-title":"FEBS J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3390\/cancers2020498","article-title":"Possible DNA viral factors of human breast cancer","volume":"2","author":"Hsu","year":"2010","journal-title":"Cancers"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/jmcb\/mjy063","article-title":"Assembly of a parts list of the human mitotic cell cycle machinery","volume":"11","author":"Giotti","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1006\/viro.1999.0146","article-title":"Herpes Simplex Virus Infection Blocks Events in the G1 Phase of the Cell Cycle","volume":"267","author":"Song","year":"2000","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Noguchi, E., and Gadaleta, M.C. (2014). Cell Cycle Regulation During Viral Infection. Cell Cycle Control: Mechanisms and Protocols, Springer.","DOI":"10.1007\/978-1-4939-0888-2"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhang, B., Li, Y., Yang, P., He, S., Li, W., Li, M., Hu, Q., and Zhang, M. (2024). Herpes Simplex Virus Type 2 Blocks IFN-\u03b2 Production through the Viral UL24 N-Terminal Domain-Mediated Inhibition of IRF-3 Phosphorylation. Viruses, 16.","DOI":"10.3390\/v16101601"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13918","DOI":"10.1128\/JVI.01615-14","article-title":"Molecular Requirement for Sterols in Herpes Simplex Virus Entry and Infectivity","volume":"88","author":"Wudiri","year":"2014","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00445-17","DOI":"10.1128\/JVI.00445-17","article-title":"Cellular Cholesterol Facilitates the Postentry Replication Cycle of Herpes Simplex Virus 1","volume":"91","author":"Wudiri","year":"2017","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.cmet.2011.02.004","article-title":"Regulation of Lipid Homeostasis by the Bifunctional SREBF2-miR33a Locus","volume":"13","author":"Bommer","year":"2011","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1161\/CIRCULATIONAHA.113.002714","article-title":"Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility","volume":"128","author":"Xiao","year":"2013","journal-title":"Circulation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100411","DOI":"10.1016\/j.jlr.2023.100411","article-title":"SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6","volume":"64","author":"Fowler","year":"2023","journal-title":"J. Lipid Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1016\/j.cell.2015.11.045","article-title":"Limiting cholesterol biosynthetic flux spontaneously engages type I IFN signaling","volume":"163","author":"York","year":"2015","journal-title":"Cell"},{"key":"ref_55","unstructured":"National Health Research Ethics Council (2024). South African Ethics in Health Research Guidelines: Principles, Processes and Structures, NdoH."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/8\/795\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:26:59Z","timestamp":1760034419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/8\/795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["pathogens14080795"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14080795","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2025,8,8]]}}}