{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:53:14Z","timestamp":1785268394885,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T00:00:00Z","timestamp":1537228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["D92F16000490005"],"award-info":[{"award-number":["D92F16000490005"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) is a highly prevalent opportunistic agent in the world population, which persists as a latent virus after a primary infection. Besides the well-established role of this agent causing severe diseases in immunocompromised individuals, more recently, HCMV has been evoked as a possible factor contributing to the pathogenesis of autoimmune diseases such as systemic sclerosis (SSc). The interplay between HCMV and immune surveillance is supposed to become unbalanced in SSc patients with expanded anti-HCMV immune responses, which are likely involved in the exacerbation of inflammatory processes. In this study, blood samples from a cohort of SSc patients vs. healthy subjects were tested for anti-HCMV immune responses (IgM, IgG antibodies, and T cells to peptide pools spanning the most immunogenic HCMV proteins). Statistically significant increase of HCMV-specific CD8+ T cell responses in SSc patients vs. healthy subjects was observed. Moreover, significantly greater HCMV-specific CD8+ T cell responses were found in SSc patients with a longer disease duration and those with higher modified Rodnan skin scores. Given the known importance of T cells in the development of SSc and that this virus may contribute to chronic inflammatory diseases, these data support a relevant role of HCMV-specific CD8+ T cell responses in SSc pathogenesis.<\/jats:p>","DOI":"10.3390\/v10090508","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T11:52:29Z","timestamp":1537271549000},"page":"508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Paradigmatic Interplay between Human Cytomegalovirus and Host Immune System: Possible Involvement of Viral Antigen-Driven CD8+ T Cell Responses in Systemic Sclerosis"],"prefix":"10.3390","volume":"10","author":[{"given":"Maria-Cristina","family":"Arcangeletti","sequence":"first","affiliation":[{"name":"Virology Unit, University-Hospital of Parma, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Maccari","sequence":"additional","affiliation":[{"name":"Virology Unit, University-Hospital of Parma, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Vescovini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-6217","authenticated-orcid":false,"given":"Riccardo","family":"Volpi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilia","family":"Giuggioli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, University-Hospital Policlinico of Modena, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Sighinolfi","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, University-Hospital Policlinico of Modena, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"De Conto","sequence":"additional","affiliation":[{"name":"Virology Unit, University-Hospital of Parma, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Chezzi","sequence":"additional","affiliation":[{"name":"Virology Unit, University-Hospital of Parma, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Calderaro","sequence":"additional","affiliation":[{"name":"Virology Unit, University-Hospital of Parma, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clodoveo","family":"Ferri","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, University-Hospital Policlinico of Modena, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/00005792-200203000-00004","article-title":"Systemic Sclerosis Study Group of the Italian Society of Rheumatology (SIR-GSSSc). Systemic sclerosis: Demographic, clinical, and serologic features and survival in 1012 Italian patients","volume":"81","author":"Ferri","year":"2002","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0889-857X(03)00023-1","article-title":"Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being","volume":"29","author":"Medsger","year":"2003","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1056\/NEJMra0806188","article-title":"Scleroderma","volume":"360","author":"Gabrielli","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.autrev.2014.08.029","article-title":"Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients\u2019 population and review of the literature","volume":"13","author":"Ferri","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_5","first-page":"S3","article-title":"One year in review 2017: Systemic sclerosis","volume":"35","author":"Barsotti","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Giuggioli, D., Colaci, M., Cocchiara, E., Spinella, A., Lumetti, F., and Ferri, C. (2018). From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution. Dermatol. Res. Pract., 2018.","DOI":"10.1155\/2018\/6984282"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/1346-8138.14153","article-title":"Systemic sclerosis","volume":"45","author":"Asano","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/art.20315","article-title":"Is systemic sclerosis an antigen-driven T cell disease?","volume":"50","author":"Sakkas","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/16066350500095415","article-title":"New developments in the pathogenesis of systemic sclerosis","volume":"38","author":"Sakkas","year":"2005","journal-title":"Autoimmunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"iii3","DOI":"10.1093\/rheumatology\/ken481","article-title":"Overview of pathogenesis of systemic sclerosis","volume":"48","author":"Abraham","year":"2006","journal-title":"Rheumatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.autrev.2010.09.010","article-title":"Do infections facilitate the emergence of systemic sclerosis?","volume":"10","author":"Grossman","year":"2011","journal-title":"Autoimmun. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.imlet.2017.10.002","article-title":"Current perspectives on the role of CD8+ T cells in systemic sclerosis","volume":"195","author":"Fuschiotti","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1046\/j.1365-2249.2002.02017.x","article-title":"Abnormal expression of intracellular cytokines and chemokine receptors in peripheral blood T lymphocytes from patients with systemic sclerosis","volume":"130","author":"Fujii","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Radstake, T., van Bon, L., Broen, J., Hussiani, A., Hesselstrand, R., Wuttge, D., Deng, Y., Simms, R., Lubberts, E., and Lafyatis, R. (2009). The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGF\u03b2 and IFN\u03b3 distinguishes SSc phenotypes. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005903"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.autrev.2010.08.003","article-title":"Relationship between cytokine profiles and clinical outcomes in patients with systemic sclerosis","volume":"10","author":"Baraut","year":"2010","journal-title":"Autoimmun. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.clim.2011.01.013","article-title":"Alteration of Th17 and Treg cell subpopulations co-exist in patients affected with systemic sclerosis","volume":"139","author":"Fenoglio","year":"2011","journal-title":"Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R166","DOI":"10.1186\/ar3486","article-title":"Increased frequency of circulating Th22 in addition to Th17 and Th2 lymphocytes in systemic sclerosis: Association with interstitial lung disease","volume":"13","author":"Truchetet","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1093\/rheumatology\/kes090","article-title":"T cells in systemic sclerosis: A reappraisal","volume":"51","author":"Hugle","year":"2012","journal-title":"Rheumatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R151","DOI":"10.1186\/ar4334","article-title":"Th17 cells favor inflammatory responses while inhibiting type I collagen deposition by dermal fibroblasts: Differential effects in healthy and systemic sclerosis fibroblasts","volume":"15","author":"Brembilla","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cytogfr.2015.12.002","article-title":"New insights into CD4+ T cell abnormalities in systemic sclerosis","volume":"28","author":"Liu","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"84","DOI":"10.5493\/wjem.v7.i3.84","article-title":"Treg\/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients","volume":"7","author":"Krasimirova","year":"2017","journal-title":"World J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.jid.2016.11.037","article-title":"Skin-resident effector memory CD8+CD28\u2013 T cells exhibit a profibrotic phenotype in patients with systemic sclerosis","volume":"137","author":"Li","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/art.37706","article-title":"Interleukin-13-producing CD8+ T cells mediate dermal fibrosis in patients with systemic sclerosis","volume":"65","author":"Fuschiotti","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.jid.2017.02.968","article-title":"Toxic Memories in Systemic Sclerosis","volume":"137","author":"Duffy","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1136\/ard.49.1.40","article-title":"Increase in activated T cells and reduction in suppressor inducer T cells in systemic sclerosis","volume":"49","author":"Gustafsson","year":"1990","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1046\/j.1365-2362.1999.00434.x","article-title":"T-cell receptor gene usage in patients with fibrosing alveolitis and control subjects","volume":"29","author":"Lympany","year":"1999","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/j.1365-2249.2004.02647.x","article-title":"T cell repertoire in patients with stable scleroderma","volume":"139","author":"Tiev","year":"2005","journal-title":"Clin. Exp. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.autrev.2008.07.022","article-title":"Systemic sclerosis and infections","volume":"8","author":"Randone","year":"2008","journal-title":"Autoimmun. Rev."},{"key":"ref_29","first-page":"3","article-title":"Role of viral infections in the etiopathogenesis of systemic sclerosis","volume":"31","author":"Moroncini","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/472978","article-title":"Human cytomegalovirus and autoimmune disease","volume":"2014","author":"Halenius","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1099\/0022-1317-76-4-741","article-title":"Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues","volume":"76","author":"Sinzger","year":"1995","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.autrev.2017.05.024","article-title":"The role of endothelial cells in the vasculopathy of systemic sclerosis: A systematic review","volume":"16","author":"Mostmans","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_33","first-page":"94","article-title":"Antibodies against Human Cytomegalovirus in the Pathogenesis of Systemic Sclerosis: A Gene Array Approach","volume":"3","author":"Lunardi","year":"2006","journal-title":"PLoS Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/j.1749-6632.2009.04808.x","article-title":"The role of infections in the immunopathogensis of systemic sclerosis-evidence from serological studies","volume":"1173","author":"Arnson","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s10067-017-3553-5","article-title":"Human cytomegalovirus (HCMV) UL44 and UL57 specific antibody responses in anti-HCMV-positive patients with systemic sclerosis","volume":"36","author":"Marou","year":"2017","journal-title":"Clin. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.4049\/jimmunol.179.6.4283","article-title":"Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects","volume":"179","author":"Vescovini","year":"2007","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s12026-011-8251-9","article-title":"Buffered memory: A hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection","volume":"51","author":"Snyder","year":"2011","journal-title":"Immunol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00430-012-0273-y","article-title":"Viral latency drives \u201cmemory inflation\u201d: A unifying hypothesis linking two hallmarks of cytomegalovirus infection","volume":"201","author":"Seckert","year":"2012","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s11357-013-9594-z","article-title":"Na\u00efve and memory CD8 T cell pool homeostasis in advanced aging: Impact of age and of antigen-specific responses to cytomegalovirus","volume":"36","author":"Vescovini","year":"2014","journal-title":"Age"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.exger.2014.03.020","article-title":"New advances in CMV and immunosenescence","volume":"55","author":"Sansoni","year":"2014","journal-title":"Exp. Gerontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nri.2016.38","article-title":"T cell responses to cytomegalovirus","volume":"16","author":"Klenerman","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1002\/art.38098","article-title":"2013 classification criteria for systemic sclerosis: An American College of Rheumatology\/European League against Rheumatism collaborative initiative","volume":"65","author":"Khanna","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_43","first-page":"1281","article-title":"Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis","volume":"22","author":"Clements","year":"1995","journal-title":"J. Rheumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5301\/jsrd.5000231","article-title":"Standardization of the modified Rodnan skin score for use in clinical trials of systemic sclerosis","volume":"2","author":"Khanna","year":"2017","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_45","unstructured":"Maccari, C., Vescovini, R., and Arcangeletti, M.-C. (2018). Unpublished work."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1136\/ard.61.10.937","article-title":"Systemic sclerosis following human cytomegalovirus infection","volume":"61","author":"Ferri","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/80533","article-title":"Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegalovirus late protein UL94 and induce apoptosis in human endothelial cells","volume":"6","author":"Lunardi","year":"2000","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s11357-017-9986-6","article-title":"CMV immune evasion and manipulation of the immune system with aging","volume":"39","author":"Jackson","year":"2017","journal-title":"Geroscience"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s11357-017-9982-x","article-title":"A constant companion: Immune recognition and response to cytomegalovirus with aging and implications for immune fitness","volume":"39","author":"Souquette","year":"2017","journal-title":"Geroscience"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2217\/fvl.12.8","article-title":"The immune response to human CMV","volume":"7","author":"Diamond","year":"2012","journal-title":"Future Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.3390\/v4071116","article-title":"T cell memory in the context of persistent herpes viral infections","volume":"4","author":"Torti","year":"2012","journal-title":"Viruses"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.exger.2004.04.004","article-title":"Different contribution of EBV and CMV infections in very long-term carriers to age-related alterations of CD8+ T cells","volume":"39","author":"Vescovini","year":"2004","journal-title":"Exp. Gerontol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1136\/thorax.55.11.958","article-title":"Involvement of Epstein-Barr virus latent membrane protein 1 in disease progression in patients with idiopathic pulmonary fibrosis","volume":"55","author":"Tsukamoto","year":"2000","journal-title":"Thorax"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13075-017-1237-9","article-title":"Epstein-Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes","volume":"19","author":"Farina","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Cicin-Sain, L., Brien, J., Uhrlaub, J., Drabig, A., Marandu, T., and Nikolich-Zugich, J. (2012). Cytomegalovirus Infection Impairs Immune Responses and Accentuates T-cell Pool Changes Observed in Mice with Aging. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002849"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.micpath.2018.04.041","article-title":"Cytomegalovirus aggravates the autoimmune phenomenon in systemic autoimmune diseases","volume":"120","author":"Janahi","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0022-1759(01)00416-1","article-title":"Use of overlapping peptide mixtures as antigens for cytokine flow cytometry","volume":"255","author":"Maecker","year":"2001","journal-title":"J. Immunol. Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1046\/j.1365-2249.2003.02266.x","article-title":"Population analysis of antiviral T cell responses using MHC class I-peptide tetramers","volume":"134","author":"Komatsu","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1479-5876-5-17","article-title":"CMV pp65 and IE-1 T cell epitopes recognized by healthy subjects","volume":"5","author":"Slezak","year":"2007","journal-title":"J. Transl. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11539","DOI":"10.1128\/JVI.01016-06","article-title":"Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive monocyte extravasation and transfer of productive virus to enhance hematogenous dissemination of HCMV","volume":"80","author":"Bentz","year":"2006","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1159\/000150501","article-title":"Latent and persistent infections of monocytes and macrophages","volume":"39","author":"Sinclair","year":"1996","journal-title":"Intervirology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s12985-016-0634-z","article-title":"Human cytomegalovirus reactivation from latency: Validation of a \u201cswitch\u201d model in vitro","volume":"13","author":"Arcangeletti","year":"2016","journal-title":"Virol. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1128\/JVI.78.9.4444-4453.2004","article-title":"Human cytomegalovirus induces monocyte differentiation and migration as a strategy for dissemination and persistence","volume":"78","author":"Smith","year":"2004","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1097\/00007890-199807150-00011","article-title":"Cytolytic activity against allogeneic human endothelia: Resistance of cytomegalovirus-infected cells and virally activated lysis of uninfected cells","volume":"66","author":"Waldman","year":"1998","journal-title":"Transplantation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"652","DOI":"10.7326\/0003-4819-97-5-652","article-title":"D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): A retrospective analysis","volume":"97","author":"Steen","year":"1982","journal-title":"Ann. Intern. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1002\/1529-0131(200011)43:11<2445::AID-ANR11>3.0.CO;2-Q","article-title":"Skin thickness score as a predictor and correlate of outcome in systemic sclerosis: High-dose versus low-dose penicillamine trial","volume":"43","author":"Clements","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1002\/1529-0131(200112)44:12<2828::AID-ART470>3.0.CO;2-U","article-title":"Improvement in skin thickening in systemic sclerosis associated with improved survival","volume":"44","author":"Steen","year":"2001","journal-title":"Arthritis Rheum."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1002\/art.22721","article-title":"Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: Application of a latent linear trajectory model","volume":"56","author":"Shand","year":"2007","journal-title":"Arthritis Rheum."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/9\/508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:21:16Z","timestamp":1760196076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/9\/508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,18]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["v10090508"],"URL":"https:\/\/doi.org\/10.3390\/v10090508","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,18]]}}}