{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:11:51Z","timestamp":1784542311003,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL-6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virus-specific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR\u2012 groups. The number of synovial CD4-positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR\u2012 group. CD4- and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR\u2012 groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.<\/jats:p>","DOI":"10.3390\/ijms21176004","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T09:35:31Z","timestamp":1597916131000},"page":"6004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection"],"prefix":"10.3390","volume":"21","author":[{"given":"Valerija","family":"Groma","sequence":"first","affiliation":[{"name":"Joint Laboratory of Electron Microscopy, Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda blvd 9, LV-1010 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihails","family":"Tarasovs","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Electron Microscopy, Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda blvd 9, LV-1010 Riga, Latvia"},{"name":"Department of Internal Diseases, Riga Stradins University, Hipokrata str. 2, LV-1038 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Skuja","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Electron Microscopy, Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda blvd 9, LV-1010 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofija","family":"Semenistaja","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Electron Microscopy, Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda blvd 9, LV-1010 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0594-1091","authenticated-orcid":false,"given":"Zaiga","family":"Nora-Krukle","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, Riga Stradins University, Ratsupites str. 5, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-6390","authenticated-orcid":false,"given":"Simons","family":"Svirskis","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, Riga Stradins University, Ratsupites str. 5, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-1784","authenticated-orcid":false,"given":"Modra","family":"Murovska","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, Riga Stradins University, Ratsupites str. 5, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/papr.12551","article-title":"Degenerative Joint Diseases and Neuroinflammation","volume":"17","author":"Fusco","year":"2017","journal-title":"Pain Pract."},{"key":"ref_2","first-page":"347","article-title":"One year in review 2018: Novelties in the treatment of rheumatoid arthritis","volume":"36","author":"Bortoluzzi","year":"2018","journal-title":"Clin. 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