title: Hantavirus-infection confers resistance to cytotoxic lymphocyte-mediated apoptosis.
abstract: Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS; also called hantavirus pulmonary syndrome (HPS)), both human diseases with high case-fatality rates. Endothelial cells are the main targets for hantaviruses. An intriguing observation in patients with HFRS and HCPS is that on one hand the virus infection leads to strong activation of CD8 T cells and NK cells, on the other hand no obvious destruction of infected endothelial cells is observed. Here, we provide an explanation for this dichotomy by showing that hantavirus-infected endothelial cells are protected from cytotoxic lymphocyte-mediated induction of apoptosis. When dissecting potential mechanisms behind this phenomenon, we discovered that the hantavirus nucleocapsid protein inhibits the enzymatic activity of both granzyme B and caspase 3. This provides a tentative explanation for the hantavirus-mediated block of cytotoxic granule-mediated apoptosis-induction, and hence the protection of infected cells from cytotoxic lymphocytes. These findings may explain why infected endothelial cells in hantavirus-infected patients are not destroyed by the strong cytotoxic lymphocyte response.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Shawon
authors.initials: S
authors.lastname: Gupta
authors.forename: Monika
authors.initials: M
authors.lastname: Braun
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Tischler
authors.forename: Malin
authors.initials: M
authors.lastname: Stoltz
authors.forename: Karin B
authors.initials: KB
authors.lastname: Sundström
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Björkström
authors.forename: Hans-Gustaf
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: Jonas
authors.initials: J
authors.lastname: Klingström
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D015550:Cell Degranulation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D053804:Granzymes / Q000037:antagonists & inhibitors; D006476:Orthohantavirus / Q000276:immunology*; D018778:Hantavirus Infections / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D061945:Caspase Inhibitors; D053804:Granzymes; D053148:Caspase 3
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