The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome
Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors. The aim of this study was to determine the involvement of human herpesvirus (HHV)-6A/B, HHV-7, and parvovi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-03887-0 |
| _version_ | 1797945730362507264 |
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| author | Santa Rasa-Dzelzkaleja Angelika Krumina Svetlana Capenko Zaiga Nora-Krukle Sabine Gravelsina Anda Vilmane Lauma Ievina Yehuda Shoenfeld Modra Murovska the VirA project |
| author_facet | Santa Rasa-Dzelzkaleja Angelika Krumina Svetlana Capenko Zaiga Nora-Krukle Sabine Gravelsina Anda Vilmane Lauma Ievina Yehuda Shoenfeld Modra Murovska the VirA project |
| author_sort | Santa Rasa-Dzelzkaleja |
| collection | DOAJ |
| description | Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors. The aim of this study was to determine the involvement of human herpesvirus (HHV)-6A/B, HHV-7, and parvovirus B19 (B19V) in the etiopathogenesis of ME/CFS. Methods 200 patients with clinically diagnosed ME/CFS and 150 apparently healthy individuals were enrolled in this study. Single-round, nested, and quantitative real-time polymerase chain reactions (PCR) were used to detect the presence and load of HHV-6A/B, HHV-7, and B19V. HHV-6A and HHV-6B were distinguished by PCR and restriction analysis. Immunoenzymatic assays were applied to estimate the presence of virus-specific antibodies and the level of cytokines. Results HHV-6A/B, HHV-7, and B19V specific antibodies were detected among patients and healthy individuals in 92.1% and 76.7%, 84.6% and 93.8%, and 78% and 67.4% of cases. HHV-6B had 99% of HHV-6 positive patients. Latent HHV-6A/B, HHV-7, and B19V infection/co-infection was observed in 51.5% of the patients and 76.7% of the healthy individuals, whereas active–45% of the ME/CFS patients and 8.7% of healthy individuals. HHV-6A/B load in patients with a persistent infection/co-infection in a latent and active phase was 262 and 653.2 copies/106 cells, whereas HHV-7 load was 166.5 and 248.5 copies/106 cells, and B19V-96.8 and 250.8 copies/106 cells, respectively. ME/CFS patients with persistent infection in an active phase had a higher level of pro-inflammatory cytokines (interleukin(IL)-6, tumor necrosis factor-alpha(TNF-α) and IL-12) and anti-inflammatory (IL-10) than with a persistent infection in a latent phase. A significant difference was revealed in the levels of TNF-α, IL-12, and IL-10 among the patient groups without infection, with latent infection/co-infection, active single, double and triple co-infection. The levels of TNF-α, IL-12, and IL-10 are significantly higher in patients with severe compared with a moderate course of ME/CFS. Conclusions Significantly more persistent HHV-6A/B, HHV-7, and B19V infection/co-infection in an active phase with a higher viral load and elevated levels of pro- and anti-inflammatory cytokines among patients with ME/CFS than healthy individuals indicate the importance of these infections/co-infections in ME/CFS development. The presence of these infections/co-infections influences the ME/CFS clinical course severity. |
| first_indexed | 2024-04-10T20:59:44Z |
| format | Article |
| id | doaj.art-44c1d6a796304447af54f35ed05b6ac4 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-10T20:59:44Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-44c1d6a796304447af54f35ed05b6ac42023-01-22T12:23:28ZengBMCJournal of Translational Medicine1479-58762023-01-0121111210.1186/s12967-023-03887-0The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndromeSanta Rasa-Dzelzkaleja0Angelika Krumina1Svetlana Capenko2Zaiga Nora-Krukle3Sabine Gravelsina4Anda Vilmane5Lauma Ievina6Yehuda Shoenfeld7Modra Murovska8the VirA projectInstitute of Microbiology and Virology, Rīga Stradiņš UniversityFaculty of Medicine, Department of Infectology, Rīga Stradiņš UniversityInstitute of Microbiology and Virology, Rīga Stradiņš UniversityInstitute of Microbiology and Virology, Rīga Stradiņš UniversityInstitute of Microbiology and Virology, Rīga Stradiņš UniversityInstitute of Microbiology and Virology, Rīga Stradiņš UniversityInstitute of Microbiology and Virology, Rīga Stradiņš UniversityZabludowicz Center for Autoimmune Diseases, Sheba Medical CentreInstitute of Microbiology and Virology, Rīga Stradiņš UniversityAbstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors. The aim of this study was to determine the involvement of human herpesvirus (HHV)-6A/B, HHV-7, and parvovirus B19 (B19V) in the etiopathogenesis of ME/CFS. Methods 200 patients with clinically diagnosed ME/CFS and 150 apparently healthy individuals were enrolled in this study. Single-round, nested, and quantitative real-time polymerase chain reactions (PCR) were used to detect the presence and load of HHV-6A/B, HHV-7, and B19V. HHV-6A and HHV-6B were distinguished by PCR and restriction analysis. Immunoenzymatic assays were applied to estimate the presence of virus-specific antibodies and the level of cytokines. Results HHV-6A/B, HHV-7, and B19V specific antibodies were detected among patients and healthy individuals in 92.1% and 76.7%, 84.6% and 93.8%, and 78% and 67.4% of cases. HHV-6B had 99% of HHV-6 positive patients. Latent HHV-6A/B, HHV-7, and B19V infection/co-infection was observed in 51.5% of the patients and 76.7% of the healthy individuals, whereas active–45% of the ME/CFS patients and 8.7% of healthy individuals. HHV-6A/B load in patients with a persistent infection/co-infection in a latent and active phase was 262 and 653.2 copies/106 cells, whereas HHV-7 load was 166.5 and 248.5 copies/106 cells, and B19V-96.8 and 250.8 copies/106 cells, respectively. ME/CFS patients with persistent infection in an active phase had a higher level of pro-inflammatory cytokines (interleukin(IL)-6, tumor necrosis factor-alpha(TNF-α) and IL-12) and anti-inflammatory (IL-10) than with a persistent infection in a latent phase. A significant difference was revealed in the levels of TNF-α, IL-12, and IL-10 among the patient groups without infection, with latent infection/co-infection, active single, double and triple co-infection. The levels of TNF-α, IL-12, and IL-10 are significantly higher in patients with severe compared with a moderate course of ME/CFS. Conclusions Significantly more persistent HHV-6A/B, HHV-7, and B19V infection/co-infection in an active phase with a higher viral load and elevated levels of pro- and anti-inflammatory cytokines among patients with ME/CFS than healthy individuals indicate the importance of these infections/co-infections in ME/CFS development. The presence of these infections/co-infections influences the ME/CFS clinical course severity.https://doi.org/10.1186/s12967-023-03887-0Myalgic encephalomyelitis/chronic fatigue syndrome,HHV-6AHHV-6BHHV-7Human parvovirus B19 |
| spellingShingle | Santa Rasa-Dzelzkaleja Angelika Krumina Svetlana Capenko Zaiga Nora-Krukle Sabine Gravelsina Anda Vilmane Lauma Ievina Yehuda Shoenfeld Modra Murovska the VirA project The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome Journal of Translational Medicine Myalgic encephalomyelitis/chronic fatigue syndrome, HHV-6A HHV-6B HHV-7 Human parvovirus B19 |
| title | The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome |
| title_full | The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome |
| title_fullStr | The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome |
| title_full_unstemmed | The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome |
| title_short | The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome |
| title_sort | persistent viral infections in the development and severity of myalgic encephalomyelitis chronic fatigue syndrome |
| topic | Myalgic encephalomyelitis/chronic fatigue syndrome, HHV-6A HHV-6B HHV-7 Human parvovirus B19 |
| url | https://doi.org/10.1186/s12967-023-03887-0 |
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