Hantavirus-infection Confers Resistance to Cytotoxic Lymphocyte-Mediated Apoptosis

PLoS Pathogens

Nicole D. Tischler¹  Hans-Gustaf Ljunggren²  Shawon Gupta²  Karin B. Sundström²  Jonas Klingström³  Monika Braun³  Niklas K. Björkström³  Malin Stoltz⁴ 

[1] Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden;Fundación Ciencia & Vida, Santiago, Chile

关键词: Nucleocapsids;    Endothelial cells;    Apoptosis;    Andes virus;    NK cells;    Recombinant proteins;    Hantavirus;    Lymphocytes;   

DOI  :  10.1371/journal.ppat.1003272

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY