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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Brisse, Ellen Imbrechts, Maya Mitera, Tania Vandenhaute, Jessica Wouters, Carine H. Snoeck, Robert Andrei, Graciela Matthys, Patrick |
| Abstract | Background Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder caused by unbridled activation of T cells and macrophages, culminating in a life-threatening cytokine storm. A genetic and acquired subtype are distinguished, termed primary and secondary HLH, respectively. Clinical manifestations of both forms are frequently preceded by a viral infection, predominantly with herpesviruses. The exact role of the viral infection in the development of the hemophagocytic syndrome remains to be further elucidated. Methods We utilized a recently developed murine model of cytomegalovirus-associated secondary HLH and dissected the respective contributions of lytic viral replication and immunopathology in its pathogenesis. Results HLH-like disease only developed in cytomegalovirus-susceptible mouse strains unable to clear the virus, but the severity of symptoms was not correlated to the infectious viral titer. Lytic viral replication and sustained viremia played an essential part in the pathogenesis since abortive viral infection was insufficient to induce a full-blown HLH-like syndrome. Nonetheless, a limited set of symptoms, in particular anemia, thrombocytopenia and elevated levels of soluble CD25, appeared less dependent of the viral replication but rather mediated by the host’s immune response, as corroborated by immunosuppressive treatment of infected mice with dexamethasone. Conclusion Both virus-mediated pathology and immunopathology cooperate in the pathogenesis of full-blown virus-associated secondary HLH and are closely entangled. A certain level of viremia appears necessary to elicit the characteristic HLH-like symptoms in the model. |
| Related Links | https://virologyj.biomedcentral.com/counter/pdf/10.1186/s12985-017-0908-0.pdf |
| Ending Page | 16 |
| Page Count | 16 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12985-017-0908-0 |
| Journal | Virology Journal |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2017-12-19 |
| Access Restriction | Open |
| Subject Keyword | Virology Hemophagocytic lymphohistiocytosis HLH macrophage activation syndrome MAS mouse model mouse cytomegalovirus MCMV immunopathology virus-mediated pathology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Virology Infectious Diseases |
| Journal Impact Factor | 4/2023 |
| 5-Year Journal Impact Factor | 3.8/2023 |
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