Pathology of Puumala hantavirus infection in macaques.

Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland.
PLoS ONE (Impact Factor: 3.53). 02/2008; 3(8):e3035. DOI: 10.1371/journal.pone.0003035
Source: PubMed

ABSTRACT Hantaviruses are globally important human pathogens that cause hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Capillary leakage is central to hantaviral diseases, but how it develops, has remained unknown. It has been hypothesized that the pathogenesis of hantavirus infection would be a complex interplay between direct viral effects and immunopathological mechanisms. Both of these were studied in the so far best model of mild hemorrhagic fever with renal syndrome, i.e. cynomolgus macaques infected with wild-type Puumala hantavirus. Viral RNA detected by in situ hybridization and nucleocapsid protein detected by immunohistochemical staining were observed in kidney, spleen and liver tissues. Inflammatory cell infiltrations and tubular damage were found in the kidneys, and these infiltrations contained mainly CD8-type T-cells. Importantly, these results are consistent with those obtained from patients with hantaviral disease, thus showing that the macaque model of hantavirus infection mimics human infection also on the tissue level. Furthermore, both the markers of viral replication and the T-cells appeared to co-localize in the kidneys to the sites of tissue damage, suggesting that these two together might be responsible for the pathogenesis of hantavirus infection.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease characterized by acute onset, fever, malaise, and back pain. As the disease progresses, hemorrhagic disturbances and kidney dysfunctions predominate. The examination of tissue collected postmortem supports the premise that virus replication is not responsible for this pathology; therefore, it is widely believed that virus-induced immune responses lead to the clinical manifestations associated with HFRS. The overproduction of inflammatory cytokines is commonly reported in subjects with HFRS and has given rise to the hypothesis that a so-called "cytokine storm" may play a pivotal role in the pathogenesis of this disease. Currently, supportive care remains the only effective treatment for HFRS. Our data show that serum levels of interferon (IFN)-γ, interleukin (IL)-10, CCL2, and IL-12 are upregulated in HFRS cases when compared to healthy controls and the level of upregulation is dependent on the phase and severity of the disease. Furthermore, we observed an association between the mild form of the disease and elevated serum levels of IFN-γ and IL-12. Collectively, these observations suggest that the administration of exogenous IFN-γ and IL-12 may provide antiviral benefits for the treatment of HFRS and, thus, warrants further investigations.
    European Journal of Clinical Microbiology 06/2014; · 3.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is probably multifactorial. We aimed to evaluate the possible spleen enlargement during acute PUUV infection, and to determine its association with thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5-8 months later. The change in spleen length was compared with markers describing the severity of the disease. In all patients, the spleen length was increased in the acute phase compared with the control phase (median 129 mm vs 111 mm, p < 0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p = 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but not with maximum serum creatinine level or minimum platelet count. Enlarged spleen, evaluated by MRI, was shown to be a common finding during acute PUUV infection. However, it does not associate with thrombocytopenia and acute kidney injury.
    Scandinavian journal of infectious diseases. 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nephropathia epidemica, a zoonosis caused by Hantavirus infection (most commonly subtype Puumala) is associated with flu-like symptoms and acute kidney failure. Kidney manifestations are characterized predominantly by tubulointerstitial nephritis, hemorrhage into medullary tissues, interstitial edema, and tubular cell necrosis. Kidney failure is accompanied by proteinuria, and in some cases, nephrotic-range proteinuria may occur. However, the cellular mechanisms of proteinuria remain to be elucidated. We describe a Hantavirus (Puumala) infection in a 27-year-old man with acute kidney failure and severe and rapidly reversible proteinuria. Light microscopy of a kidney biopsy specimen showed only minor changes of glomeruli. However, transmission electron microscopy revealed podocyte foot-process effacement. Immunofluorescence staining of the slit diaphragm protein podocin and the tight junction protein ZO-1 revealed a partial mislocalization of these proteins. Together, these findings highlight that Hantavirus infection may perturb podocyte integrity, resulting in glomerular proteinuria. These alterations of podocytes and consequently the glomerular filtration barrier may be transient and resolve within weeks.
    American Journal of Kidney Diseases 06/2014; · 5.76 Impact Factor

Full-text (2 Sources)

Available from
May 29, 2014