title: Viral load and immune response dynamics in patients with haemorrhagic fever with renal syndrome.
abstract: Haemorrhagic fever with renal syndrome (HFRS) in Slovenia can be caused by infection with either Dobrava (DOBV) or Puumala (PUUV) virus, but a clear difference in disease severity is observed. We hypothesized that the wide spectrum of disease observed among HFRS patients might be related to differing immune responses and viral load kinetics. To test this hypothesis we analysed sequential blood samples from 29 HFRS patients hospitalized in Slovenia. Measuring viral RNA in patient samples revealed that viraemia lasts for longer than previously believed, with DOBV or PUUV-infected patients having viraemias lasting on average 30 days or 16 days, respectively. DOBV-infected patients were found to have a higher viral load than the PUUV-infected patients (10(7) vs. 10(5) RNA copies/mL). Both DOBV and PUUV-infected patients had IgM at the time of hospital admission, but there was a difference in IgG antibody dynamics, with only a minority of DOBV-infected patients having IgG antibodies. In our study, elevated levels of IL-10, TNF-α and IFN-γ were detected in all of the samples regardless of the causative agent. In DOBV-infected patients the decrease in cytokine secretion level appeared around day 20 post-infection, while in PUUV-infected patients the change was earlier. In general, our findings point toward notable differences between PUUV and DOBV infections, in terms of viral load and antibody and cytokine response dynamics, all of which may be reflected in differing disease severities and clinical outcomes.
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Korva
authors.forename: A
authors.initials: A
authors.lastname: Saksida
authors.forename: N
authors.initials: N
authors.lastname: Kejžar
authors.forename: C
authors.initials: C
authors.lastname: Schmaljohn
authors.forename: T
authors.initials: T
authors.lastname: Avšič-Županc
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D001769:Blood / Q000276:immunology* / Q000821:virology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D017524:Slovenia; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019562:Viral Load; D014766:Viremia
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Cytokines; dynamic; hantavirus; humoral response; serial samples