{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:30:54Z","timestamp":1767713454397,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cCEINGE TASK-FORCE COVID19\u201d, Regione Campania","award":["D64I200003800"],"award-info":[{"award-number":["D64I200003800"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P \u2264 1 \u00d7 10\u22125) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.<\/jats:p>","DOI":"10.3390\/ijms22105372","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T06:13:45Z","timestamp":1621491225000},"page":"5372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6173-281X","authenticated-orcid":false,"given":"Sueva","family":"Cantalupo","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito Alessandro","family":"Lasorsa","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-7721","authenticated-orcid":false,"given":"Roberta","family":"Russo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immacolata","family":"Andolfo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"D\u2019Alterio","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara Eleni","family":"Rosato","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3487-7743","authenticated-orcid":false,"given":"Giulia","family":"Frisso","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Abete","sequence":"additional","affiliation":[{"name":"COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, 80042 Boscotrecase, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian Marco","family":"Cassese","sequence":"additional","affiliation":[{"name":"COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, 80042 Boscotrecase, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Servillo","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Gentile","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Clinica e Chirurgia, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmelo","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetics Unit, A.O.R.N. \u2018Antonio Cardarelli\u2019, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Della Monica","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetics Unit, A.O.R.N. \u2018Antonio Cardarelli\u2019, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"AORN dei Colli Presidio Ospedaliero Cotugno, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Russo","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Radiologia, Casa di Cura Villa dei Fiori, 80011 Acerra, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pellegrino","family":"Cerino","sequence":"additional","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Buonerba","sequence":"additional","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-3014","authenticated-orcid":false,"given":"Biancamaria","family":"Pierri","sequence":"additional","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy"},{"name":"Dipartimento di Medicina, Chirurgia e Odontoiatria \u201cScuola Medica Salernitana\u201d, Universit\u00e0 di Salerno, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0970-7243","authenticated-orcid":false,"given":"Massimo","family":"Zollo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-0356","authenticated-orcid":false,"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-1259","authenticated-orcid":false,"given":"Mario","family":"Capasso","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80136 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1620\/tjem.250.271","article-title":"The Coronavirus Disease 2019 (COVID-19) Pandemic","volume":"250","author":"Baloch","year":"2020","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1056\/NEJMcp2009575","article-title":"Severe Covid-19","volume":"383","author":"Berlin","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1056\/NEJMoa2004500","article-title":"Covid-19 in Critically Ill Patients in the Seattle Region\u2014Case Series","volume":"382","author":"Bhatraju","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1016\/j.jinf.2020.04.021","article-title":"Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis","volume":"81","author":"Zheng","year":"2020","journal-title":"J. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1056\/NEJMoa2020283","article-title":"Genomewide Association Study of Severe Covid-19 with Respiratory Failure","volume":"383","author":"Ellinghaus","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-020-03065-y","article-title":"Genetic mechanisms of critical illness in COVID-19","volume":"591","author":"Clohisey","year":"2021","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Bastard, P., Liu, Z., Le Pen, J., Moncada-Velez, M., Chen, J., Ogishi, M., Sabli, I.K.D., Hodeib, S., and Korol, C. (2020). Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science, 370.","DOI":"10.1126\/science.abd4570"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ng.840","article-title":"Principles for the post-GWAS functional characterization of cancer risk loci","volume":"43","author":"Freedman","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"E4762","DOI":"10.1073\/pnas.1423228112","article-title":"Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor","volume":"112","author":"Gornalusse","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1073\/pnas.94.5.1925","article-title":"The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes","volume":"94","author":"Bleul","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R525","DOI":"10.1152\/ajpregu.00019.2019","article-title":"CCR5 is a required signaling receptor for macrophage expression of inflammatory genes in response to viral double-stranded RNA","volume":"316","author":"Shaheen","year":"2019","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.humimm.2017.10.001","article-title":"Frequencies of gene variant CCR5-Delta32 in 87 countries based on next-generation sequencing of 1.3 million individuals sampled from 3 national DKMS donor centers","volume":"78","author":"Solloch","year":"2017","journal-title":"Hum. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/nm1196-1240","article-title":"The role of a mutant CCR5 allele in HIV-1 transmission and disease progression","volume":"2","author":"Huang","year":"1996","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1515\/med-2018-0062","article-title":"The CCR5-Delta32 Genetic Polymorphism and HIV-1 Infection Susceptibility: A Meta-analysis","volume":"13","author":"Ni","year":"2018","journal-title":"Open Med. (Wars.)"},{"key":"ref_16","first-page":"5447","article-title":"Maraviroc: A review of its use in HIV infection and beyond","volume":"9","author":"Woollard","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.4049\/jimmunol.173.5.3287","article-title":"CCR5-deficient mice control Mycobacterium tuberculosis infection despite increased pulmonary lymphocytic infiltration","volume":"173","author":"Algood","year":"2004","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1016\/S0002-9440(10)65068-7","article-title":"Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus","volume":"156","author":"Dawson","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10048-006-0032-6","article-title":"Gene expression analyses reveal molecular relationships among 20 regions of the human CNS","volume":"7","author":"Roth","year":"2006","journal-title":"Neurogenetics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"D52","DOI":"10.1093\/nar\/gkx1017","article-title":"3DIV: A 3D-genome Interaction Viewer and database","volume":"46","author":"Yang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shelton, J.F., Shastri, A.J., Ye, C., Weldon, C.H., Filshtein-Sonmez, T., Coker, D., Symons, A., Esparza-Gordillo, J., The 23andMe COVID-19 Team, and Aslibekyan, S. (2021). Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity. Nat. Genet.","DOI":"10.1101\/2020.09.04.20188318"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"W314","DOI":"10.1093\/nar\/gku411","article-title":"DUET: A server for predicting effects of mutations on protein stability using an integrated computational approach","volume":"42","author":"Pires","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Daga, S., Fallerini, C., Baldassarri, M., Fava, F., Valentino, F., Doddato, G., Benetti, E., Furini, S., Giliberti, A., and Tita, R. (2021). Employing a systematic approach to biobanking and analyzing clinical and genetic data for advancing COVID-19 research. Eur. J. Hum. Genet.","DOI":"10.1101\/2020.07.24.20161307"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ajhg.2020.08.007","article-title":"The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature","volume":"107","author":"LoPresti","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"872","DOI":"10.3389\/fgene.2020.00872","article-title":"Genetic Analysis of the Coronavirus SARS-CoV-2 Host Protease TMPRSS2 in Different Populations","volume":"11","author":"Russo","year":"2020","journal-title":"Front. Genet."},{"key":"ref_26","first-page":"102322","article-title":"Common variants at 21q22.3 locus influence MX1 gene expression and susceptibility to severe COVID-19","volume":"24","author":"Andolfo","year":"2020","journal-title":"medRxiv"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.cyto.2013.08.008","article-title":"Genetic diversity and linkage disequilibrium in the chemokine receptor CCR2-CCR5 region among individuals and populations","volume":"64","author":"Lawhorn","year":"2013","journal-title":"Cytokine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1742-6405-3-22","article-title":"Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals","volume":"3","author":"Trecarichi","year":"2006","journal-title":"AIDS Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1016\/j.jmb.2018.06.027","article-title":"CCR5 Revisited: How Mechanisms of HIV Entry Govern AIDS Pathogenesis","volume":"430","author":"Brelot","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41586-020-2818-3","article-title":"The major genetic risk factor for severe COVID-19 is inherited from Neanderthals","volume":"587","author":"Zeberg","year":"2020","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hoover, K.C. (2018). Intragenus (Homo) variation in a chemokine receptor gene (CCR5). PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204989"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0002-9440(10)64378-7","article-title":"Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes","volume":"160","author":"Kunkel","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1084\/jem.20042530","article-title":"Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection","volume":"202","author":"Glass","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.immuni.2008.05.011","article-title":"The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections","volume":"29","author":"Kohlmeier","year":"2008","journal-title":"Immunity"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1046\/j.1523-1755.1998.00211.x","article-title":"Chemokine receptor (CCR5) expression in human kidneys and in the HIV infected macaque","volume":"54","author":"Eitner","year":"1998","journal-title":"Kidney Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0165-5728(00)00371-4","article-title":"Astrocytes express functional chemokine receptors","volume":"111","author":"Dorf","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/s41598-018-19643-0","article-title":"CCR5\/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells","volume":"8","author":"Singh","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S0165-5728(00)00274-5","article-title":"Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue","volume":"108","author":"Simpson","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pathak, G.A., Singh, K., Miller-Fleming, T.W., Wendt, F., Ehsan, N., Hou, K., Johnson, R., Lu, Z., Gopalan, S., and Dimbou, L.Y. (2020). Integrative analyses identify susceptibility genes underlying COVID-19 hospitalization. medRxiv.","DOI":"10.1101\/2020.12.07.20245308"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e166","DOI":"10.1038\/emm.2015.33","article-title":"CTCF as a multifunctional protein in genome regulation and gene expression","volume":"47","author":"Kim","year":"2015","journal-title":"Exp. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2009.06.001","article-title":"CTCF: Master weaver of the genome","volume":"137","author":"Phillips","year":"2009","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"104512","DOI":"10.1016\/j.meegid.2020.104512","article-title":"Chemokine receptor gene polymorphisms and COVID-19: Could knowledge gained from HIV\/AIDS be important?","volume":"85","author":"Mehlotra","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/S0140-6736(98)04158-0","article-title":"CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS)","volume":"352","author":"McDermott","year":"1998","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/s41590-019-0406-1","article-title":"CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome","volume":"20","author":"Kulkarni","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1084\/jem.20051970","article-title":"CCR5 deficiency increases risk of symptomatic West Nile virus infection","volume":"203","author":"Glass","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/s12974-015-0447-9","article-title":"CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system","volume":"12","author":"Durrant","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1099\/vir.0.000165","article-title":"CCR5 deficiency predisposes to fatal outcome in influenza virus infection","volume":"96","author":"Falcon","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/s41591-020-1038-6","article-title":"A dynamic COVID-19 immune signature includes associations with poor prognosis","volume":"26","author":"Laing","year":"2020","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"63","DOI":"10.11648\/j.ajcem.20160403.15","article-title":"Polymorphism in Regulatory T-cell (Treg)-Related Genes Is Associated with Unexplained Recurrent Pregnancy Loss","volume":"4","author":"Sharif","year":"2016","journal-title":"Am. J. Clin. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/382722a0","article-title":"Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene","volume":"382","author":"Samson","year":"1996","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41431-020-0636-6","article-title":"The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic","volume":"28","author":"Initiative","year":"2020","journal-title":"Eur. J. Hum. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:04:32Z","timestamp":1760162672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22105372"],"URL":"https:\/\/doi.org\/10.3390\/ijms22105372","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,5,20]]}}}