Hantavirus regulation of endothelial cell functions

Erich R. Mackow; Irina N. Gavrilovskaya

doi:10.1160/TH09-09-0640

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(06): 1030-1041
DOI: 10.1160/TH09-09-0640

Theme Issue Article

Schattauer GmbH

Hantavirus regulation of endothelial cell functions

Erich R. Mackow

¹Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA

,

Irina N. Gavrilovskaya

²Northport VAMC, Northport, New York, USA

› Author Affiliations

Abstract

Summary

Hantaviruses cause two vascular permeability-based diseases and primarily infect endothelial cells which form the primary fluid barrier of the vasculature. Since hantavirus infections are not lytic, the mechanisms by which hantaviruses cause haemorrhagic fever with renal syndrome (HFRS) or Hantavirus Pulmonary Syndrome (HPS) are indeterminate. HPS is associated with acute pulmonary oedema and HFRS with moderate haemorrhage and renal sequelae, perhaps reflecting the location of vast microvascular beds and endothelial cell reservoirs available for hantavirus infection. Endothelial cells regulate capillary integrity, and hantavirus infection provides a primary means for alteing vascular permeability that contributes to pathogenesis. The central importance of endothelial cells in regulating oedema, vascular repair, angiogenesis, immune cell recruitment, platelet deposition as well as gas exchange and solute delivery suggest that a multitude of inputs and cellular responses may be influenced by hantavirus infection and contribute to pathogenic changes in vascular permeability. Here we focus on understanding hantavirus interactions with endothelial cells which are linked to vascular permeability, and provide insight into the contribution of endothelial cell responses in hantavirus pathogenesis.

Keywords

Virology - endothelial cells - integrins - hypoxia - chemokines

Full Text

References

References
1 Acevedo LM. et al. Semaphorin 3A suppresses VEGF-mediated angiogenesis yet acts as a vascular permeability factor. Blood 2008; 111: 2674-2680.
2 Alff PJ. et al. The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1-directed interferon responses. J Virol 2006; 80: 9676-9686.
3 Alff PJ. et al. The NY-1 hantavirus Gn cytoplasmic tail coprecipitates TRAF3 and inhibits cellular interferon responses by disrupting TBK1-TRAF3 complex formation. J Virol 2008; 82: 9115-9122.
4 Artoni A. et al. Integrin beta3 regions controlling binding of murine mAb 7E3: implications for the mechanism of integrin alphaIIbbeta3 activation. Proc Natl Acad Sci USA 2004; 101: 13114-13120.
5 Baffert F. et al. Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules. Am J Physiol Heart Circ Physiol 2006; 290: H107-118.
6 Baker EK. et al. A genetic analysis of integrin function: Glanzmann thrombasthenia in vitro. Proc Natl Acad Sci USA 1997; 94: 1973-1978.
7 Banno A, Ginsberg MH. Integrin activation. Biochem Soc Trans 2008; 36: 229-234.
8 Bates DO. et al. Regulation of microvascular permeability by vascular endothelial growth factors. J Anat 2002; 200: 581-597.
9 Baumgartner-Parzer SM, Waldhausl WK. The endothelium as a metabolic and endocrine organ: its relation with insulin resistance. Exp Clin Endocrinol Diabetes 2001; 109 (Suppl. 02) S166-179.
10 Berger MM. et al. Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema. Am J Respir Crit Care Med 2005; 172: 763-767.
11 Bernatchez PN. et al. Vascular endothelial growth factor effect on endothelial cell proliferation, migration, and platelet-activating factor synthesis is Flk-1-dependent. J Biol Chem 1999; 274: 31047-31054.
12 Billecocq AM. et al. NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription. J Virol 2004; 78: 9798-9806.
13 Blakqori GS. et al. La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts. J Virol 2007; 81: 4991-4999.
14 Borges EY. et al. Platelet-derived growth factor receptor beta and vascular endothelial growth factor receptor 2 bind to the beta 3 integrin through its extracellular domain. J Biol Chem 2000; 275: 39867-39873.
15 Brakenhielm E. Substrate matters: reciprocally stimulatory integrin and VEGF signaling in endothelial cells. Circ Res 2007; 101: 536-538.
16 Bridgen A, Elliott RM. Rescue of a segmented negative-strand RNA virus entirely from cloned complementary DNAs. Proc Natl Acad Sci USA 1996; 93: 15400-15404.
17 Brinkmann V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther 2007; 115: 84-105.
18 Bustamante EA. et al. Pleural fluid characteristics in hantavirus pulmonary syndrome. Chest 1997; 112: 1133-1136.
19 Byzova TV. et al. A mechanism for modulation of cellular responses to VEGF: activation of the integrins. Mol Cell 2000; 06: 851-860.
20 Calvete JJ. Platelet integrin GPIIb/IIIa: structurefunction correlations. An update and lessons from other integrins. Proc Soc Exp Biol Med 1999; 222: 29-38.
21 Calvete JJ. et al. Assignment of disulphide bonds in human platelet GPIIIa. A disulphide pattern for the beta-subunits of the integrin family. Biochem J 1991; 274: 63-71.
22 Campen MJ. et al. Characterization of shock in a hamster model of hantavirus infection. Virology 2006; 356: 45-49.
23 Camps C. et al. hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 2008; 14: 1340-1348.
24 Carpenter TC. et al. Endothelin-mediated increases in lung VEGF content promote vascular leak in young rats exposed to viral infection and hypoxia. Am J Physiol Lung Cell Mol Physiol 2005; 289: L1075-1082.
25 Chang B. et al. Hantavirus cardiopulmonary syndrome. Semin Respir Crit Care Med 2007; 28: 193-200.
26 Chen JP, Cosgriff TM. Hemorrhagic fever virus-induced changes in hemostasis and vascular biology. Blood Coagul Fibrinolysis 2000; 11: 461-483.
27 Chinoy MR. et al. Angiopoietin-1 and VEGF in vascular development and angiogenesis in hypoplastic lungs. Am J Physiol Lung Cell Mol Physiol 2002; 283: L60-66.
28 Coller B. GPIIb/IIIa Antagonists: Pathophysiologic and Therapeutic insights from studies of c7E3 Fab. Thrombosis and Haemostasis 1997; 78: 730-735.
29 Coller B. Platelet GPIIb/IIIb antagonists: the first anti-integrin receptor therapeutics. J Clin Invest 1997; 99: 1467-1471.
30 Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 2008; 112: 3011-3025.
31 Corada M. et al. Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci USA 1999; 96: 9815-9820.
32 Corada M. et al. A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability. Blood 2002; 100: 905-911.
33 Cosgriff TM. Mechanisms of disease in Hantavirus infection: pathophysiology of hemorrhagic fever with renal syndrome. Rev Infect Dis 1991; 13: 97-107.
34 Cosgriff TM. et al. Platelet dysfunction contributes to the haemostatic defect in haemorrhagic fever with renal syndrome. Trans R Soc Trop Med Hyg 1991; 85: 660-663.
35 Cosgriff TM, Lewis RM. Mechanisms of disease in hemorrhagic fever with renal syndrome. Kidney Int Suppl 1991; 35: S72-79.
36 Custer DM. et al. Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine. J Virol 2003; 77: 9894-9905.
37 Dehler M. et al. Hypoxia causes permeability oedema in the constant-pressure perfused rat lung. Eur Respir J 2006; 27: 600-606.
38 Dejana E. et al. The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci 2008; 121: 2115-2122.
39 Dietl CA. et al. Extracorporeal membrane oxygenation support improves survival of patients with severe Hantavirus cardiopulmonary syndrome. J Thorac Cardiovasc Surg 2008; 135: 579-584.
40 Divakaran V, Mann DL. The emerging role of microRNAs in cardiac remodeling and heart failure. Circ Res 2008; 103: 1072-1083.
41 Duchin JS. et al. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group [see comments]. N Engl J Med 1994; 330: 949-955.
42 Dvorak HF. Discovery of vascular permeability factor (VPF). Exp Cell Res 2006; 312: 522-526.
43 Dvorak HF. et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995; 146: 1029-1039.
44 Dvorak HF. et al. Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med 1991; 174: 1275-1278.
45 Elliott LH. et al. Isolation of the causative agent of hantavirus pulmonary syndrome. Am J Trop Med Hyg 1994; 51: 102-108.
46 Emeny JM, Morgan MJ. Regulation of the interferon system: evidence that Vero cells have a genetic defect in interferon production. J Gen Virol 1979; 43: 247-252.
47 Ennis FA. et al. Hantavirus pulmonary syndrome: CD8+ and CD4+ cytotoxic T lymphocytes to epitopes on Sin Nombre virus nucleocapsid protein isolated during acute illness. Virology 1997; 238: 380-390.
48 Enria D. et al. Hantavirus pulmonary syndrome in Argentina. Possibility of person to person transmission. Medicina 1996; 56: 709-711.
49 Esser S. et al. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci 1998; 111: 1853-1865.
50 Fasanaro PY. et al. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 2008; 283: 15878-15883.
51 Fedorchenko IL. Serum level of various biologically active substances and their connection with vessel permeability in hemorrhagic fever with kidney syndrome. Vopr Med Khim 1991; 37: 70-72.
52 Fedorchenko IL. et al. Vascular permeability, microcirculation and biologically active substances in patients with hemorrhagic fever with renal syndrome. Ter Arkh 1990; 62: 71-74.
53 Fish JE. et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 2008; 15: 272-284.
54 Flick K. et al. Rescue of Hantaan virus minigenomes. Virology 2003; 306: 219-224.
55 French DL, Coller BS. Hematologically important mutations: Glanzmann thrombasthenia. Blood Cells Mol Dis 1997; 23: 39-51.
56 Gamble JR. et al. Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions. Circ Res 2000; 87: 603-607.
57 Garcia JG. et al. Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J Clin Invest 2001; 108: 689-701.
58 Gavard J, Gutkind JS. VEGF controls endothelialcell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol 2006; 08: 1223-1234.
59 Gavard J. et al. Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia. Dev Cell 2008; 14: 25-36.
60 Gavrilovskaya I. et al. New York 1 and Sin Nombre viruses are serotypically distinct viruses associated with hantavirus pulmonary syndrome. J Clin Microbiol 1999; 37: 122-126.
61 Gavrilovskaya I. et al. Pathogenic hantaviruses selectively inhibit beta-3 integrin directed endothelial cell migration. Arch. Virol 2002; 147: 1913-1931.
62 Gavrilovskaya I. et al. Determination of specific immune complexes and dynamics of their circulation in patients suffering from hemorrhagic fever with a renal syndrome. Microbiol J 1987; 49: 71-76.
63 Gavrilovskaya IN. et al. Cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by beta3 integrins. J Virol 1999; 73: 3951-3959.
64 Gavrilovskaya IN. et al. Hantaviruses direct endothelial cell permeability by sensitizing cells to the vascular permeability factor VEGF, while angiopoietin 1 and sphingosine 1-phosphate inhibit hantavirus-directed permeability. J Virol 2008; 82: 5797-5806.
65 Gavrilovskaya IN. et al. beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure. Proc Natl Acad Sci USA 1998; 95: 7074-7079.
66 Geimonen E. et al. Tyrosine residues direct the ubiquitination and degradation of the NY-1 hantavirus G1 cytoplasmic tail. J Virol 2003; 77: 10760-10868.
67 Geimonen E. et al. Hantavirus pulmonary syndrome-associated hantaviruses contain conserved and functional ITAM signaling elements. J Virol 2003; 77: 1638-1643.
68 Geimonen E. et al. Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses. Proc Natl Acad Sci USA 2002; 99: 13837-13842.
69 Goldsmith CS. et al. Ultrastructural characteristics of Sin Nombre virus, causative agent of hantavirus pulmonary syndrome. Arch Virol 1995; 140: 2107-2122.
70 Groeneveld AB. Vascular pharmacology of acute lung injury and acute respiratory distress syndrome. Vascul Pharmacol 2002; 39: 247-256.
71 Hacker H. et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 2006; 439: 204-207.
72 Handke W. et al. Hantaan virus triggers TLR3-dependent innate immune responses. J Immunol 2009; 182: 2849-2858.
73 Hayasaka D. et al. Increased permeability of human endothelial cell line EA.hy926 induced by hantavirusspecific cytotoxic T lymphocytes. Virus Res 2007; 123: 120-127.
74 He JQ. et al. Specificity of TRAF3 in its negative regulation of the noncanonical NF-kappa B pathway. J Biol Chem 2007; 282: 3688-3694.
75 Hewat EA. et al. Architecture of the VE-cadherin hexamer. J Mol Biol 2007; 365: 744-751.
76 Heyman PA. et al. Hantavirus infections in Europe: from virus carriers to a major public-health problem. Expert Rev Anti Infect Ther 2009; 07: 205-217.
77 Hippenstiel S. et al. VEGF induces hyperpermeability by a direct action on endothelial cells. Am J Physiol 1998; 274: L678-684.
78 Hiscott J. Triggering the innate antiviral response through IRF-3 activation. J Biol Chem 2007; 282: 15325-15329.
79 Hjelle B. et al. Molecular linkage of hantavirus pulmonary syndrome to the white-footed mouse, Peromyscus leucopus: genetic characterization of the M genome of New York virus. J Virol 1995; 69: 8137-8141.
80 Hodivala-Dilke KM. et al. Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 1999; 103: 229-238.
81 Holmes K. et al. Vascular endothelial growth factor receptor-2: Structure, function, intracellular signalling and therapeutic inhibition. Cell Signal 2007; 19: 2003-2012.
82 Hooper JW. et al. DNA vaccination with the Hantaan virus M gene protects Hamsters against three of four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in Rhesus monkeys. J Virol 2001; 75: 8469-8477.
83 Hooper JW. et al. DNA vaccination with hantavirus M segment elicits neutralizing antibodies and protects against seoul virus infection. Virology 1999; 255: 269-278.
84 Hooper JW. et al. A lethal disease model for hantavirus pulmonary syndrome. Virology 2001; 289: 6-14.
85 Hopkins SR. et al. Pulmonary blood flow heterogeneity during hypoxia and high-altitude pulmonary edema. Am J Respir Crit Care Med 2005; 171: 83-87.
86 Hornung V. et al. 5’-Triphosphate RNA is the ligand for RIG-I. Science 2006; 314: 994-997.
87 Hwang JY. et al. Reduced expression of angiopoietin-1 in Hantaan virus-infected human umbilical vein endothelial cell increases their permeability. Acta Virol 2009; 53: 7-13.
88 Hynes RO. Structural biology. Changing partners. Science 2003; 300: 755-756.
89 Hynes RO. et al. Integrins in vascular development. Braz J Med Biol Res 1999; 32: 501-510.
90 Hynes RO, Hodivala-Dilke KM. Insights and questions arising from studies of a mouse model of Glanzmann thrombasthenia. Thromb Haemost 1999; 82: 481-485.
91 Igarashi J. et al. VEGF induces S1P1 receptors in endothelial cells: Implications for cross-talk between sphingolipid and growth factor receptors. Proc Natl Acad Sci USA 2003; 100: 10664-10669.
92 Jaaskelainen KM. et al. Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter. J Med Virol 2007; 79: 1527-1536.
93 Jain RK, Munn LL. Leaky vessels?. Call Ang1! Nat Med 2000; 06: 131-132.
94 Jho D. et al. Angiopoietin-1 opposes VEGF-induced increase in endothelial permeability by inhibiting TRPC1-dependent Ca2 influx. Circ Res 2005; 96: 1282-1290.
95 Jiang H. et al. Hantaan virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon, interleukin-6 and tumor necrosis factor-alpha. Virology 2008; 380: 52-59.
96 Jokinen EJ. et al. Nephropathia epidemica: immunohistochemical study of pathogenesis. Clin Nephrol 1978; 09: 1-5.
97 Jonsson CB. et al. Treatment of hantavirus pulmonary syndrome. Antiviral Res 2008; 78: 162-169.
98 Joutsi-Korhonen L. et al. The effect of recombinant IgG antibodies against the leucine-33 form of the platelet beta3 integrin (HPA-1a) on platelet function. Thromb Haemost 2004; 91: 743-754.
99 Kanerva M. et al. Pathogenesis of puumala and other hantavirus infections. Rev Med Virol 1998; 08: 67-86.
100 Kayagaki N. et al. DUBA: a deubiquitinase that regulates type I interferon production. Science 2007; 318: 1628-1632.
101 Kevil CG. et al. Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins. J Biol Chem 1998; 273: 15099-15103.
102 Khaiboullina SF. et al. Effects of tumor necrosis factor alpha on sin nombre virus infection in vitro. J Virol 2000; 74: 11966-11971.
103 Khaiboullina SF. et al. Regulation of cellular gene expression in endothelial cells by sin nombre and prospect hill viruses. Viral Immunol 2004; 17: 234-251.
104 Kilpatrick ED. et al. Role of specific CD8+ T cells in the severity of a fulminant zoonotic viral hemorrhagic fever, hantavirus pulmonary syndrome. J Immunol 2004; 172: 3297-3304.
105 Kim HK. et al. Platelet microparticles induce angiogenesis in vitro. Br J Haematol 2004; 124: 376-384.
106 Kim IW. et al. Interferon-stimulated genes response in endothelial cells following Hantaan virus infection. J Korean Med Sci 2007; 22: 987-992.
107 Koster F. et al. Rapid presumptive diagnosis of hantavirus cardiopulmonary syndrome by peripheral blood smear review. Am J Clin Pathol 2001; 116: 665-672.
108 Krakauer T. et al. Serum levels of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 in hemorrhagic fever with renal syndrome. Viral Immunol 1995; 08: 75-79.
109 Krakauer T. et al. Serum levels of alpha and gamma interferons in hemorrhagic fever with renal syndrome. Viral Immunol 1994; 07: 97-101.
110 Kraus AA. et al. Differential antiviral response of endothelial cells after infection with pathogenic and nonpathogenic hantaviruses. J Virol 2004; 78: 6143-6150.
111 Kronemann N. et al. Aggregating human platelets stimulate expression of vascular endothelial growth factor in cultured vascular smooth muscle cells through a synergistic effect of transforming growth factorbeta(1) and platelet-derived growth factor(AB). Circulation 1999; 100: 855-860.
112 Kuehbacher A. et al. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res 2007; 101: 59-68.
113 Lahdevirta J. Clinical features of HFRS in Scandinavia as compared with East Asia. Scand J Infect Dis 1982; (Suppl. 36) 93-95.
114 Lahdevirta J. et al. Hantaan virus is related to hemorrhagic fever with renal syndrome in Norway. Lancet 1982; 02: 606.
115 Lampugnani MG, Dejana E. Adherens junctions in endothelial cells regulate vessel maintenance and angiogenesis. Thromb Res 2007; 120 (Suppl. 02) S1-6.
116 Lampugnani MG, Dejana E. The control of endothelial cell functions by adherens junctions. Novartis Found Symp 2007; 283 4-17 238-241.
117 Larson RS. et al. Peptide antagonists that inhibit Sin Nombre virus and hantaan virus entry through the beta3-integrin receptor. J Virol 2005; 79: 7319-7326.
118 Lee H. et al. Isolation of the etiologic agent of Korean hemorrhagic fever. J Infect Dis 1978; 137: 298-308.
119 Lee HW. Hemorrhagic fever with renal syndrome (HFRS). Scand J Infect Dis 1982; (Suppl. 36) 82-85.
120 Linderholm M. et al. Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome. J Infect Dis 1996; 173: 38-43.
121 Lowen AC. et al. Efficient bunyavirus rescue from cloned cDNA. Virology 2004; 330: 493-500.
122 Luo BH. et al. Rationally designed integrin beta3 mutatants stabilized in the high affinity conformation. J Biol Chem 2009; 284: 3917-3924.
123 Luo BH. et al. Locking the beta 3 integrin I-like domain into high and low affinity conformations with disulfides. J Biol Chem. 2004 279-10215-10221.
124 Mackow ER, Gavrilovskaya IN. Cellular receptors and hantavirus pathogenesis. Curr Top Microbiol Immunol 2001; 256: 91-115.
125 Maes PJ. et al. Hantaviruses: immunology, treatment, and prevention. Viral Immunol 2004; 17: 481-497.
126 Maes P. et al. Tumor necrosis factor-alpha genetic predisposing factors can influence clinical severity in nephropathia epidemica. Viral Immunol 2006; 19: 558-564.
127 Mahabeleshwar GH. et al. Integrin signaling is critical for pathological angiogenesis. J Exp Med 2006; 203: 2495-2507.
128 Mahabeleshwar GH. et al. Mechanisms of integrinvascular endothelial growth factor receptor cross-activation in angiogenesis. Circ Res 2007; 101: 570-580.
129 Maniatis T. et al. Structure and function of the interferon-beta enhanceosome. Cold Spring Harb Symp Quant Biol 1998; 63: 609-620.
130 McCarter SD. et al. Cell-based angiopoietin-1 gene therapy for acute lung injury. Am J Respir Crit Care Med 2007; 175: 1014-1026.
131 McClain DJ. et al. Clinical evaluation of a vaccinia-vectored Hantaan virus vaccine. J Med Virol 2000; 60: 77-85.
132 McElroy AK. et al. Andes virus M genome segment is not sufficient to confer the virulence associated with Andes virus in Syrian hamsters. Virology 2004; 326: 130-139.
133 McVerry BJ, Garcia JG. Endothelial cell barrier regulation by sphingosine 1-phosphate. J Cell Biochem 2004; 92: 1075-1085.
134 McVerry BJ, Garcia JG. In vitro and in vivo modulation of vascular barrier integrity by sphingosine 1-phosphate: mechanistic insights. Cell Signal 2005; 17: 131-139.
135 McVerry BJ. et al. Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. Am J Respir Crit Care Med 2004; 170: 987-993.
136 Milazzo ML. et al. Maporal viral infection in the Syrian golden hamster: a model of hantavirus pulmonary syndrome. J Infect Dis 2002; 186: 1390-1395.
137 Mir MA. et al. Storage of cellular 5’ mRNA caps in P bodies for viral cap-snatching. Proc Natl Acad Sci USA 2008; 105: 19294-19299.
138 Moreira IS. et al. Vascular endothelial growth factor (VEGF) inhibition--a critical review. Anticancer Agents Med Chem 2007; 07: 223-245.
139 Mori M. et al. High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome. J Infect Dis 1999; 179: 295-302.
140 Mukhopadhyay D. et al. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 1995; 375: 577-581.
141 Mukhopadhyay D. et al. Complexity in the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-receptors signaling. Mol Cell Biochem 2004; 264: 51-61.
142 Muller DW, Bosserhoff AK. Integrin beta 3 expression is regulated by let-7a miRNA in malignant melanoma. Oncogene 2008; 27: 6698-6706.
143 Nair V, Zavolan M. Virus-encoded microRNAs: novel regulators of gene expression. Trends Microbiol 2006; 14: 169-175.
144 Nawroth R. et al. VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. Embo J 2002; 21: 4885-4895.
145 Neufeld G. et al. Vascular endothelial growth factor (VEGF) and its receptors. Faseb J 1999; 13: 9-22.
146 Nichol ST. et al. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness [see comments]. Science 1993; 262: 914-917.
147 Niikura M. et al. Modification of endothelial cell functions by Hantaan virus infection: prolonged hyperpermeability induced by TNF-alpha of hantaan virusinfected endothelial cell monolayers. Arch Virol 2004; 149: 1279-1292.
148 Nolte KB. et al. Hantavirus pulmonary syndrome in the United States: a pathological description of a disease caused by a new agent. Human Pathology 1995; 26: 110-120.
149 Oganesyan G. et al. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 2006; 439: 208-211.
150 Olsson AK. et al. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 2006; 07: 359-371.
151 Otrock ZK. et al. Vascular endothelial growth factor family of ligands and receptors: review. Blood Cells Mol Dis 2007; 38: 258-268.
152 Pensiero MN, Hay J. The Hantaan virus M-segment glycoproteins G1 and G2 can be expressed independently. J Virol 1992; 66: 1907-1914.
153 Pensiero MN. et al. Expression of the Hantaan virus M genome segment by using a vaccinia virus recombinant. J Virol 1988; 62: 696-702.
154 Pensiero MN. et al. Hantaan virus infection of human endothelial cells. J Virol 1992; 66: 5929-5936.
155 Penttinen K. et al. Circulating immune complexes, immunoconglutinins, and rheumatoid factors in nephropathia epidemica. J Infect Dis 1981; 143: 15-21.
156 Pham I. et al. Hypoxia upregulates VEGF expression in alveolar epithelial cells in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 2002; 283: L1133-1142.
157 Pizurki L. et al. Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. Br J Pharmacol 2003; 139: 329-336.
158 Plyusnin A. et al. Tula virus: a newly detected hantavirus carried by European common voles. J Virol 1994; 68: 7833-7839.
159 Pomerantz JL, Baltimore D. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. Embo J 1999; 18: 6694-6704.
160 Prescott JB. et al. Early innate immune responses to Sin Nombre hantavirus occur independently of IFN regulatory factor 3, characterized pattern recognition receptors, and viral entry. J Immunol 2007; 179: 1796-1802.
161 Qi P. et al. Virus-encoded microRNAs: future therapeutic targets?. Cell Mol Immunol 2006; 03: 411-419.
162 Rasche FM. et al. Thrombocytopenia and acute renal failure in Puumala hantavirus infections. Emerg Infect Dis 2004; 10: 1420-1425.
163 Raymond T. et al. Pathogenic hantaviruses bind plexin-semaphorin-integrin domains present at the apex of inactive, bent alphavbeta3 integrin conformers. Proc Natl Acad Sci USA 2005; 102: 1163-1168.
164 Reynolds LE. et al. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 2002; 08: 27-34.
165 Rhee JS. et al. The functional role of blood platelet components in angiogenesis. Thromb Haemost 2004; 92: 394-402.
166 Ridley AJ. et al. Cell migration: integrating signals from front to back. Science 2003; 302: 1704-1709.
167 Robinson SD. et al. Beta3-integrin regulates vascular endothelial growth factor-A-dependent permeability. Arterioscler Thromb Vasc Biol 2004; 24: 2108-2114.
168 Rozman P. Platelet antigens. The role of human platelet alloantigens (HPA) in blood transfusion and transplantation. Transpl Immunol 2002; 10: 165-181.
169 Sarnow P. et al. MicroRNAs: expression, avoidance and subversion by vertebrate viruses. Nat Rev Microbiol 2006; 04: 651-659.
170 Satchell SC. et al. Angiopoietin 1 and vascular endothelial growth factor modulate human glomerular endothelial cell barrier properties. J Am Soc Nephrol 2004; 15: 566-574.
171 Satchell SC, Mathieson PW. Angiopoietins: microvascular modulators with potential roles in glomerular pathophysiology. J Nephrol 2003; 16: 168-178.
172 Schafer R. et al. Impaired VE-cadherin/beta-catenin expression mediates endothelial cell degeneration in dilated cardiomyopathy. Circulation 2003; 108: 1585-1591.
173 Schaphorst KL. et al. Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products. Am J Physiol Lung Cell Mol Physiol 2003; 285: L258-267.
174 Schmaljohn AL. et al. Isolation and initial characterization of a newfound hantavirus from California. Virology 1995; 206: 963-972.
175 Schmaljohn C. Bunyaviridae and their Replication. In: Fields ed. Virology. vol. 1 LipppincottRaven, Philadelphia: 2001: 1581-1602.
176 Schmaljohn C, Hjelle B. Hantaviruses: a global disease problem. Emerg Infect Dis 1997; 03: 95-104.
177 Schmaljohn CS. et al. Coding strategy of the S genome segment of Hantaan virus. Virology 1986; 155: 633-643.
178 Schmaljohn CS. et al. Hantaan virus M RNA: coding strategy, nucleotide sequence, and gene order. Virology 1987; 157: 31-39.
179 Scholz T. et al. The GPIIb/IIIa antagonist eptifibatide markedly potentiates platelet-leukocyte interaction and tissue factor expression following platelet activation in whole blood in vitro. Platelets 2002; 13: 401-406.
180 Sen N. et al. Degrons at the C terminus of the pathogenic but not the nonpathogenic hantavirus G1 tail direct proteasomal degradation. J Virol 2007; 81: 4323-4330.
181 Senger DR. et al. Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am J Pathol 1996; 149: 293-305.
182 Settergren B. et al. Pathogenetic and clinical aspects of the renal involvement in hemorrhagic fever with renal syndrome. Ren Fail 1997; 19: 1-14.
183 Soldi R. et al. Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. Embo J 1999; 18: 882-892.
184 Song JW. et al. Isolation of pathogenic hantavirus from white-footed mouse (Peromyscus leucopus). Lancet 1994; 344: 1637.
185 Spik KW. et al. Mixing of M segment DNA vaccines to Hantaan virus and Puumala virus reduces their immunogenicity in hamsters. Vaccine 2008; 26: 5177-5181.
186 Spiropoulou CF. et al. Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling. J Virol 2007; 81: 2769-2776.
187 Spiropoulou CF. et al. Sin Nombre virus glycoprotein trafficking. Virology 2003; 308: 48-63.
188 Stafford P. et al. Immunologic and structural analysis of eight novel domain-deletion beta(3) integrin peptides designed for detection of HPA-1 antibodies. J Thromb Haemost 2008; 06: 366-375.
189 Stenmark KR. et al. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res 2006; 99: 675-691.
190 Stoeltzing O. et al. Angiopoietin-1 inhibits vascular permeability, angiogenesis, and growth of hepatic colon cancer tumors. Cancer Res 2003; 63: 3370-3377.
191 Suarez S, Ballmer-Hofer K. VEGF transiently disrupts gap junctional communication in endothelial cells. J Cell Sci 2001; 114: 1229-1235.
192 Suarez Y. et al. Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci USA 2008; 105: 14082-14087.
193 Sugimori T. et al. Emerging Paradigms of Integrin Ligand Binding and Activation. Kidney International 1997; 51: 1454-1462.
194 Sundstrom JB. et al. Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells. J Virol 2001; 75: 6070-6085.
195 Takagi J. et al. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 2002; 110: 599-611.
196 Takuwa Y. et al. The Edg family G protein-coupled receptors for lysophospholipids: their signaling properties and biological activities. J Biochem (Tokyo) 2002; 131: 767-771.
197 Tamura M. et al. Effects of human and murine interferons against hemorrhagic fever with renal syndrome (HFRS) virus (Hantaan virus). Antiviral Res 1987; 08: 171-178.
198 Tang N. et al. Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 2004; 06: 485-495.
199 Tani M. et al. Mechanisms of sphingosine and sphingosine 1-phosphate generation in human platelets. J Lipid Res 2005; 46: 2458-2467.
200 Taylor SL. et al. Hantaan virus nucleocapsid protein binds to importin alpha proteins and inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B. J Virol 2009; 83: 1271-1279.
201 Temonen M. et al. Cytokines, adhesion molecules, and cellular infiltration in nephropathia epidemica kidneys: an immunohistochemical study. Clin Immunol Immunopathol 1996; 78: 47-55.
202 Terajima M, Ennis FA. Quantitation of antibodybound and unbound Sin Nombre virus in the plasma of patient with hantavirus pulmonary syndrome. J Virol Methods 2003; 110: 159-162.
203 Terajima M. et al. Immunopathogenesis of hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome: Do CD8+ T cells trigger capillary leakage in viral hemorrhagic fevers?. Immunol Lett 2007; 113: 117-120.
204 Terajima M. et al. High levels of viremia in patients with the Hantavirus pulmonary syndrome. J Infect Dis 1999; 180: 2030-2034.
205 Thurston G. et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000; 06: 460-463.
206 Thurston G. et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 1999; 286: 2511-2514.
207 Toro J. et al. An outbreak of hantavirus pulmonary syndrome, Chile, 1997. Emerg Infect Dis 1998; 04: 687-694.
208 Tsou R, Isik FF. Integrin activation is required for VEGF and FGF receptor protein presence on human microvascular endothelial cells. Mol Cell Biochem 2001; 224: 81-89.
209 Tuuminen T. et al. Human CD8+ T cell memory generation in Puumala hantavirus infection occurs after the acute phase and is associated with boosting of EBVspecific CD8+ memory T cells. J Immunol 2007; 179: 1988-1995.
210 Tuvim MJ. et al. Augmented lung inflammation protects against influenza A pneumonia. PLoS ONE 2009; 04: e4176.
211 Urbich C. et al. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res 2008; 79: 581-588.
212 Valbuena G, Walker DH. The endothelium as a target for infections. Annu Rev Pathol 2006; 01: 171-198.
213 van Gils JM. et al. HPA-1a alloantibodies reduce endothelial cell spreading and monolayer integrity. Mol Immunol 2009; 46: 406-415.
214 van Hinsbergh VW, van Nieuw Amerongen GP. Endothelial hyperpermeability in vascular leakage. Vascul Pharmacol 2002; 39: 171-172.
215 Vapalahti O. et al. Isolation and characterization of Tula virus, a distinct serotype in the genus Hantavirus, family Bunyaviridae. J Gen Virol 1996; 77: 3063-3067.
216 Vapalahti O. et al. Human immune response, host genetics, and severity of disease. Curr Top Microbiol Immunol 2001; 256: 153-169.
217 Verheul HM. et al. Vascular endothelial growth factor-stimulated endothelial cells promote adhesion and activation of platelets. Blood 2000; 96: 4216-4221.
218 Victorino GP. et al. Modulation of microvascular hydraulic permeability by platelet-activating factor. J Trauma 2004; 56: 379-384.
219 Voelkel NF. et al. Vascular endothelial growth factor in the lung. Am J Physiol Lung Cell Mol Physiol 2006; 290: L209-221.
220 Wahl-Jensen V. et al. Temporal analysis of Andes virus and Sin Nombre virus infections of Syrian hamsters. J Virol 2007; 81: 7449-7462.
221 Wallez Y. et al. Angiogenesis: the VE-cadherin switch. Trends Cardiovasc Med 2006; 16: 55-59.
222 Wang S. et al. Transmission electron microscopic study of the hemorrhagic spots in patients with epidemic hemorrhagic fever in the early stage. Ultrastruct Pathol 1997; 21: 281-287.
223 Wang Y. et al. Integrins regulate VE-cadherin and catenins: dependence of this regulation on Src, but not on Ras. Proc Natl Acad Sci USA 2006; 103: 1774-1779.
224 Wang Y. et al. Opposing effect of angiopoietin-1 on VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta. J Cell Physiol 2004; 198: 53-61.
225 Wathelet MG. et al. Regulation of gene expression by cytokines and virus in human cells lacking the type-I interferon locus. Eur J Biochem 2004; 206: 901-910.
226 Watkins NA. et al. Platelet alphaIIbbeta3 recombinant autoantibodies from the B-cell repertoire of a post-transfusion purpura patient. Br J Haematol 2002; 116: 677-685.
227 Weis SM, Cheresh DA. Pathophysiological consequences of VEGF-induced vascular permeability. Nature 2005; 437: 497-504.
228 Weis SM. et al. Cooperation between VEGF and beta3 integrin during cardiac vascular development. Blood 2007; 109: 1962-1970.
229 Xiao R. et al. Sin Nombre viral RNA load in patients with hantavirus cardiopulmonary syndrome. J Infect Dis 2006; 194: 1403-1409.
230 Xiao T. et al. Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature 2004; 432: 59-67.
231 Xu M. et al. Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase. Am J Physiol Cell Physiol 2007; 293: C1309-1318.
232 Yamada KM, Even-Ram S. Integrin regulation of growth factor receptors. Nat Cell Biol 2002; 04: E75-76.
233 Yanagihara R. et al. Serological survey of Prospect Hill virus infection in indigenous wild rodents in the USA. Trans R Soc Trop Med Hyg 1987; 81: 42-45.
234 Yanagihara R, Silverman DJ. Experimental infection of human vascular endothelial cells by pathogenic and nonpathogenic hantaviruses. Arch Virol 1990; 111: 281-286.
235 Yoneyama M, Fujita T. RIG-I family RNA helicases: Cytoplasmic sensor for antiviral innate immunity. Cytokine Growth Factor Rev 2007; 18: 545-551.
236 Yoneyama M. et al. Control of IRF-3 activation by phosphorylation. J Interferon Cytokine Res 2002; 22: 73-76.
237 Zaki S. et al. Hantavirus Pulmonary Syndrome: pathogenesis of an emerging infectious disease. Am J Pathol 1995; 146: 552-579.
238 Zanetti A. et al. Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling. Arterioscler Thromb Vasc Biol 2002; 22: 617-622.
239 Zhang Y. et al. Expression of L protein of Hantaan virus 84FLi strain and its application for recovery of minigenomes. Apmis 2008; 116: 1089-1096.
240 Zhu J. et al. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 2008; 32: 849-861.