title: Loss of cell membrane integrity in puumala hantavirus-infected patients correlates with levels of epithelial cell apoptosis and perforin.
abstract: Hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome are two diseases caused by hantaviruses. Capillary leakage is a hallmark of hantavirus infection. Pathogenic hantaviruses are not cytotoxic, but elevated levels of serum lactate dehydrogenase (LDH), indicative of cellular damage, are observed in patients. We report increased levels of serum perforin, granzyme B, and the epithelial cell apoptosis marker caspase-cleaved cytokeratin-18 during Puumala hantavirus infection. Significant correlation was observed between the levels of LDH and perforin and the levels of LDH and caspase-cleaved cytokeratin-18, suggesting that tissue damage is due to an immune reaction and that epithelial apoptosis contributed significantly to the damage.
authors.affiliation: Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden. jonas.klingstrom@smi.ki.se
authors.forename: Jonas
authors.initials: J
authors.lastname: Klingström
authors.forename: Jonas
authors.initials: J
authors.lastname: Hardestam
authors.forename: Malin
authors.initials: M
authors.lastname: Stoltz
authors.forename: Bartek
authors.initials: B
authors.lastname: Zuber
authors.forename: Ake
authors.initials: A
authors.lastname: Lundkvist
authors.forename: Stig
authors.initials: S
authors.lastname: Linder
authors.forename: Clas
authors.initials: C
authors.lastname: Ahlm
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000473:pathology / Q000821:virology; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D053804:Granzymes; D006480:Hemorrhagic Fever with Renal Syndrome / Q000097:blood / Q000473:pathology*; D006801:Humans; D007633:Keratins / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008562:Membrane Glycoproteins / Q000097:blood*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D029262:Puumala virus; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007633:Keratins; D007770:L-Lactate Dehydrogenase; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D020169:Caspases