title: Hantavirus Infection Suppresses Thrombospondin-1 Expression in Cultured Endothelial Cells in a Strain-Specific Manner.
abstract: Hantavirus infection is associated with two frequently fatal diseases in humans: Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The pathogenesis of hantavirus infection is complex and not fully understood; however, it is believed to involve virus-induced hyperinflammatory immune responses. Thrombospondin-1 (THBS1) is a large homotrimeric protein that plays a putative role in regulating blood homeostasis. Hyperresponsiveness to inflammatory stimuli has also been associated with defects in the THBS1 gene. Our data suggest that hantavirus infection of human umbilical cord vein endothelial cells (HUVEC) suppress the accumulation of THBS1 in the extracellular matrix. Additionally, this suppression is dependent on virus replication, implying a direct mechanism of action. Our data also imply that the pathogenic Andes and Hantaan strains inhibit THBS1 expression while the non-pathogenic Prospect Hill strain showed little inhibition. These observations suggest that a dysregulation of THBS1 may contribute to the pathogenesis of hantavirus infection.
authors.affiliation: Nevada Center for Biomedical ResearchReno, NV, USA; Department of Genetics, Institute of Fundamental Medicine and Biology, Kazan Federal UniversityKazan, Russia.
authors.forename: Svetlana F
authors.initials: SF
authors.lastname: Khaiboullina
authors.affiliation: Nevada State Public Health Laboratory, University of Nevada, Reno School of Medicine Reno, NV, USA.
authors.forename: Sergey P
authors.initials: SP
authors.lastname: Morzunov
authors.affiliation: Department of Immunology and Microbiology, University of Nevada, Reno School of Medicine Reno, NV, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: St Jeor
authors.affiliation: Department of Genetics, Institute of Fundamental Medicine and Biology, Kazan Federal University Kazan, Russia.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
authors.affiliation: Nevada Center for Biomedical ResearchReno, NV, USA; Department of Biochemistry and Molecular Biology, University of NevadaReno, NV, USA.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Lombardi
keywords: Andes; HFRS; HPS; Hantaan; Prospect Hill; THBS1; TSP1; coagulation