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Thrombosis Journal
Published in: Thrombosis Journal 1/2018

Open Access 01-12-2018 | Review

Human blood platelets and viruses: defense mechanism and role in the removal of viral pathogens

Authors: Masresha Seyoum, Bamlaku Enawgaw, Mulugeta Melku

Published in: Thrombosis Journal | Issue 1/2018

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Abstract

Platelets are small non-nucleated cell fragments and the second most abundant cell that play crucial role in managing vascular integrity and regulating hemostasis. Recent finding shows, beyond its hemostatic function platelets also play a main role in fighting against pathogen including viruses. With their receptors, platelet interacts with viral pathogen and this interaction between platelets and viral pathogens result in activation of platelets. Activated platelet releases different molecules that have antiviral activity including kinocidins and other platelet microbicidal peptides. In addition, activated platelet has antiviral role by different mechanism including; phagocytosis of viral pathogen, produce reactive oxygen species and interact with and activate other immune cells. In other side, antiplatelet treatments are one of defending mechanism of viral pathogen. This narrative review summarizes what is known regarding the role of human platelets in fighting viral pathogen.
Literature
1.
Italiano J, Hartwig JH, Michelson A. Megakaryocyte development and platelet formation. Platelets. 2007;2:23–44.CrossRef
2.
George J. Overview of platelet structure and function. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN, editors. Hemostasis and thrombosis: basic principles and clinical practice. Philadelphia: Lippincott, Williams and Wilkins; 2001. p. 381–6.
3.
Keohane EM, Smith LJ, Walenga JM. Rodak’s hematology: clinical principles and applications. 5th ed. Rivrport lane St. Louis, Missouri: Elsevier Health Sciences; 2016.
4.
Hou Y, Carrim N, Wang Y, Gallant RC, Marshall A, Ni H. Platelets in hemostasis and thrombosis: novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. Journal of biomedical research. 2015;29(6):437.PubMedCentral
5.
Rendu F, Brohard-Bohn B. The platelet release reaction: granules' constituents, secretion and functions. Platelets. 2001;12(5):261–73.CrossRefPubMed
6.
7.
Chabert A, Hamzeh-Cognasse H, Pozzetto B, Cognasse F, Schattner M, Gomez RM, et al. Human platelets and their capacity of binding viruses: meaning and challenges? BMC Immunol. 2015;16:26.CrossRefPubMedPubMedCentral
8.
9.
Cognasse F, Nguyen KA, Damien P, McNicol A, Pozzetto B, Hamzeh-Cognasse H, et al. The inflammatory role of platelets via their TLRs and Siglec receptors. Front Immunol. 2015;6:83.CrossRefPubMedPubMedCentral
10.
Weyrich A, Lindemann S, Zimmerman G. The evolving role of platelets in inflammation. J Thromb Haemost. 2003;1(9):1897–905.CrossRefPubMed
11.
Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2013;13(1):34–45.CrossRefPubMed
12.
13.
14.
Jenne C, Urrutia R, Kubes P. Platelets: bridging hemostasis, inflammation, and immunity. Int J Lab Hematol. 2013;35(3):254–61.CrossRefPubMed
15.
Nagasawa T, Nakayasu C, Rieger AM, Barreda DR, Somamoto T, Nakao M. Phagocytosis by thrombocytes is a conserved innate immune mechanism in lower vertebrates. Front Immunol. 2014;5:445.CrossRefPubMedPubMedCentral
16.
Meseguer J, Esteban MA, Rodriguez A. Are thrombocytes and platelets true phagocytes? Microsc Res Tech. 2002;57(6):491–7.CrossRefPubMed
17.
Ali RA, Wuescher LM, Worth RG. Platelets: essential components of the immune system. Current trends in immunology. 2015;16:65–78.PubMedPubMedCentral
18.
Chaipan C, Soilleux EJ, Simpson P, Hofmann H, Gramberg T, Marzi A, et al. DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets. J Virol 2006;80(18):8951-8960. Epub 2006/08/31.
19.
20.
Parikh F. Infections and thrombocytopenia. J Assoc Physicians India. 2016;64(2):11–2.PubMed
21.
Wang CS, Yao WJ, Wang ST, Chang TT, Chou P. Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2004;39(6):790–6.CrossRef
22.
Hottz ED, Oliveira MF, Nunes PC, Nogueira RMR, Valls-de-Souza R, Da Poian AT, et al. Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases. J Thromb Haemost. 2013;11(5):951–62.CrossRefPubMedPubMedCentral
23.
Alonzo MT, Lacuesta TL, Dimaano EM, Kurosu T, Suarez LA, Mapua CA, et al. Platelet apoptosis and apoptotic platelet clearance by macrophages in secondary dengue virus infections. J Infect Dis. 2012;205(8):1321–9.CrossRefPubMed
24.
Hunelshausen P, Weber C. Platelets as immune cells. Bridging inflammation and cardiovascular disease. The review is part of a thematic series on mechanisms, models, and in vivo imaging of thrombus formation. Circ Res. 2007;100:27–40.CrossRef
25.
Andonegui G, Kerfoot SM, McNagny K, Ebbert KV, Patel KD, Kubes P. Platelets express functional toll-like receptor-4. Blood. 2005;106(7):2417–23.CrossRefPubMed
26.
D'atri LP, Etulain J, Rivadeneyra L, Lapponi MJ, Fondevila C, Schattner M. Expression and functionality of toll-like receptor 3 in the megakaryocytic lineage. J Thromb Haemost. 2013;11:514–5.
27.
Koupenova M, Vitseva O, MacKay CR, Beaulieu LM, Benjamin EJ, Mick E, et al. Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis. Blood. 2014;124(5):791–802.CrossRefPubMedPubMedCentral
28.
Shiraki R, Inoue N, Kawasaki S, Takei A, Kadotani M, Ohnishi Y, et al. Expression of toll-like receptors on human platelets. Thromb Res. 2004;113(6):379–85.CrossRefPubMed
29.
Thon JN, Peters CG, Machlus KR, Aslam R, Rowley J, Macleod H, et al. T granules in human platelets function in TLR9 organization and signaling. J Cell Biol. 2012;198(4):561–74.CrossRefPubMedPubMedCentral
30.
Garraud O, Cognasse F. Platelet toll-like receptor expression: the link between “danger” ligands and inflammation. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy). 2010;9(5):322–33.
31.
Aslam R, Speck ER, Kim M, Crow AR, Bang KW, Nestel FP, et al. Platelet toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo. Blood. 2006;107(2):637–41.CrossRefPubMed
32.
Panigrahi S, Ma Y, Hong L, Gao D, West XZ, Salomon RG, et al. Engagement of platelet toll-like receptor 9 by novel endogenous ligands promotes platelet hyper-reactivity and thrombosis. Circ Res. 2012;112(1):103–12. CIRCRESAHA. 112.274241
33.
D’ Atri LP, Schattner M. Platelet toll-like receptors in thromboinflammation. Frontiers in bioscience (Landmark edition). 2017;22:1867–83.CrossRef
34.
Martel C, Cointe S, Maurice P, Matar S, Ghitescu M, Théroux P, et al. Requirements for membrane attack complex formation and anaphylatoxins binding to collagen-activated platelets. PLoS One. 2011;6(4):e18812.CrossRefPubMedPubMedCentral
35.
Rambach G, Würzner R, Speth C. Complement: an efficient sword of innate immunity. Trends in Innate Immunity. Basel: Karger Publishers; 2008. p. 78-100.
36.
Basch RS, Dolzhanskiy A, Zhang XM, Karpatkin S. The development of human megakaryocytes. II. CD4 expression occurs during haemopoietic differentiation and is an early step in megakaryocyte maturation. Br J Haematol. 1996;94(3):433–42.CrossRefPubMed
37.
Riviere C, Subra F, Cohen-Solal K, Cordette-Lagarde V, Letestu R, Auclair C, et al. Phenotypic and functional evidence for the expression of CXCR4 receptor during Megakaryocytopoiesis. Blood. 1999;93(5):1511–23.PubMed
38.
Boukour S, Masse JM, Benit L, Dubart-Kupperschitt A, Cramer E. Lentivirus degradation and DC-SIGN expression by human platelets and megakaryocytes. J Thromb Haemost. 2006;4(2):426–35.CrossRefPubMed
39.
Gitz E, Pollitt AY, Gitz-Francois JJ, Alshehri O, Mori J, Montague S, et al. CLEC-2 expression is maintained on activated platelets and on platelet microparticles. Blood. 2014;124(14):2262–70.CrossRefPubMedPubMedCentral
40.
Kar M, Singla M, Chandele A, Kabra SK, Lodha R, Medigeshi GR. Dengue virus entry and replication does not lead to productive infection in platelets. Open forum infectious diseases. 2017;4(2):ofx051.CrossRefPubMedPubMedCentral
41.
Eggerman TL, Mondoro TH, Lozier JN, Vostal JG. Adenoviral vectors do not induce, inhibit, or potentiate human platelet aggregation. Hum Gene Ther. 2002;13(1):125–8.CrossRefPubMed
42.
Flaujac C, Boukour S, Cramer-Bordé E. Platelets and viruses: an ambivalent relationship. Cell Mol Life Sci. 2010;67(4):545–56.CrossRefPubMed
43.
Negrotto S, Jaquenod de Giusti C, Rivadeneyra L, Ure AE, Mena HA, Schattner M, et al. Platelets interact with Coxsackieviruses B and have a critical role in the pathogenesis of virus-induced myocarditis. Journal of thrombosis and haemostasis : JTH. 2015;13(2):271–82.CrossRefPubMed
44.
Padovani JL, Corvino SM, Drexler JF, Silva GF, Pardini MI, Grotto RM. In vitro detection of hepatitis C virus in platelets from uninfected individuals exposed to the virus. Rev Soc Bras Med Trop. 2013;46(2):154–5.CrossRefPubMed
45.
Zahn A, Jennings N, Ouwehand WH, Allain J-P. Hepatitis C virus interacts with human platelet glycoprotein VI. J Gen Virol. 2006;87(8):2243–51.CrossRefPubMed
46.
Silva GF, Grotto RM, Verdichio-Moraes CF, Corvino SM, Ferrasi AC, Silveira LV, et al. Human platelet antigen genotype is associated with progression of fibrosis in chronic hepatitis C. J Med Virol. 2012;84(1):56–60.CrossRefPubMed
47.
Zhou SH, Liang XH, Shao LN, Yu WJ, Zhao C, Liu M. Association of human platelet antigens polymorphisms with susceptibility to hepatitis C virus infection in Chinese population. International journal of immunogenetics. 2017;44(6):337–42.CrossRefPubMed
48.
Verdichio-Moraes CF, Toralles-Pereira C, Grotto RM, Silva GF, Pardini MI. Allelic frequencies of HPA-1 to 5 human platelet antigens in patients infected with hepatitis C virus. J Med Virol. 2009;81(4):757–9.CrossRefPubMed
49.
50.
Yeaman MR. Platelets: at the nexus of antimicrobial defence. Nat Rev Microbiol. 2014;12(6):426–37.CrossRefPubMed
51.
Witte A, Chatterjee M, Lang F, Gawaz M. Platelets as a novel source of pro-inflammatory chemokine CXCL14. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;41(4):1684–96.CrossRef
52.
Henn V, Slupsky JR, Gräfe M, Anagnostopoulos I, Förster R, Müller-Berghaus G, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature. 1998;391(6667):591–4.CrossRefPubMed
53.
Chatterjee M, von Ungern-Sternberg SN, Seizer P, Schlegel F, Buttcher M, Sindhu NA, et al. Platelet-derived CXCL12 regulates monocyte function, survival, differentiation into macrophages and foam cells through differential involvement of CXCR4-CXCR7. Cell Death Dis. 2015;6:e1989.CrossRefPubMedPubMedCentral
54.
Yount NY, Waring AJ, Gank KD, Welch WH, Kupferwasser D, Yeaman MR. Structural correlates of antimicrobial efficacy in IL-8 and related human kinocidins. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2007;1768(3):598–608.CrossRef
55.
Tsegaye TS, Gnirß K, Rahe-Meyer N, Kiene M, Krämer-Kühl A, Behrens G, et al. Platelet activation suppresses HIV-1 infection of T cells. Retrovirology. 2013;10(1):48.CrossRef
56.
Auerbach DJ, Lin Y, Miao H, Cimbro R, DiFiore MJ, Gianolini ME, et al. Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor. Proc Natl Acad Sci. 2012;109(24):9569–74.CrossRefPubMedPubMedCentral
57.
Parker ZF, Rux AH, Riblett AM, Lee FH, Rauova L, Cines DB, et al. Platelet factor 4 inhibits and enhances HIV-1 infection in a concentration-dependent manner by modulating viral attachment. AIDS Res Hum Retrovir. 2016;32(7):705–17.CrossRefPubMedPubMedCentral
58.
59.
Torre D, Pugliese A. Platelets and HIV-1 infection: old and new aspects. Curr HIV Res. 2008;6(5):411–8.CrossRefPubMed
60.
Mohan KV, Rao SS, Atreya CD. Antiviral activity of selected antimicrobial peptides against vaccinia virus. Antivir Res. 2010;86(3):306–11.CrossRefPubMed
61.
Buck CB, Day PM, Thompson CD, Lubkowski J, Lu W, Lowy DR, et al. Human α-defensins block papillomavirus infection. Proc Natl Acad Sci. 2006;103(5):1516–21.CrossRefPubMedPubMedCentral
62.
Begonja AJ, Gambaryan S, Geiger J, Aktas B, Pozgajova M, Nieswandt B, et al. Platelet NAD (P) H-oxidase–generated ROS production regulates αIIbβ3-integrin activation independent of the NO/cGMP pathway. Blood. 2005;106(8):2757–60.CrossRefPubMed
63.
Wachowicz B, Olas B, Zbikowska HM, Buczynski A. Generation of reactive oxygen species in blood platelets. Platelets. 2002;13(3):175–82.CrossRefPubMed
64.
Zander DM, Klinger M. The blood platelets contribution to innate host defense–what they have learned from their big brothers. Biotechnol J. 2009;4(6):914–26.CrossRefPubMed
65.
Tilton C, Clippinger AJ, Maguire T, Alwine JC. Human cytomegalovirus induces multiple means to combat reactive oxygen species. J Virol. 2011;85(23):12585–93.CrossRefPubMedPubMedCentral
66.
Youssefian T, Drouin A, Massé J-M, Guichard J, Cramer EM. Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood. 2002;99(11):4021–9.CrossRefPubMed
67.
Jansen AG, Low HZ, van den Brand J, van Riel D, Osterhaus A, van der Vries E. Platelets can phagocytose Influenza virus which may contribute to the occurrence of thrombocytopenia during Influenza infection. Am Soc Hematology. 2016;128(22):1358.
68.
Kullaya VI, de Mast Q, van der Ven A, El Moussaoui H, Kibiki G, Simonetti E, et al. Platelets modulate innate immune response against human respiratory syncytial virus in vitro. Viral Immunol. 2017;30(8):576–81.CrossRefPubMed
69.
Hartwell DW, Mayadas TN, Berger G, Frenette PS, Rayburn H, Hynes RO, et al. Role of P-selectin cytoplasmic domain in granular targeting in vivo and in early inflammatory responses. J Cell Biol. 1998;143(4):1129–41.CrossRefPubMedPubMedCentral
70.
Hottz ED, Medeiros-de-Moraes IM, Vieira-de-Abreu A, De Assis EF, Vals-de-Souza R, Castro-Faria-Neto HC, et al. Platelet activation and apoptosis modulate monocyte inflammatory responses in dengue. J Immunol. 2014;193(4):1864–72.CrossRefPubMedPubMedCentral
71.
Chapman LM, Aggrey AA, Field DJ, Srivastava K, Ture S, Yui K, et al. Platelets present antigen in the context of MHC class I. J Immunol. 2012;189(2):916–23.CrossRefPubMedPubMedCentral
72.
Iannacone M, Sitia G, Isogawa M, Whitmire JK, Marchese P, Chisari FV, et al. Platelets prevent IFN-α/β-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus. Proc Natl Acad Sci. 2008;105(2):629–34.CrossRefPubMedPubMedCentral
73.
Triantafilou K, Triantafilou M, Takada Y, Fernandez N. Human parechovirus 1 utilizes integrins αvβ3 and αvβ1 as receptors. J Virol. 2000;74(13):5856–62.CrossRefPubMedPubMedCentral
74.
Nelsen-Salz B, Eggers HJ, Zimmermann H. Integrin αvβ3 (vitronectin receptor) is a candidate receptor for the virulent echovirus 9 strain Barty. J Gen Virol. 1999;80(9):2311–3.CrossRefPubMed
75.
Fleming FE, Graham KL, Takada Y, Coulson BS. Determinants of the specificity of rotavirus interactions with the α2β1 integrin. J Biol Chem. 2011;286(8):6165–74.CrossRefPubMed
76.
Mackow E, Gavrilovskaya I. Cellular receptors and hantavirus pathogenesis. Hantaviruses: Springer; 2001. p. 91–115.
77.
Alvarez CP, Lasala F, Carrillo J, Muñiz O, Corbí AL, Delgado R. C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol. 2002;76(13):6841–4.CrossRefPubMedPubMedCentral
78.
Shimojima M, Ströher U, Ebihara H, Feldmann H, Kawaoka Y. Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry. J Virol. 2012;86(4):2067–78.CrossRefPubMedPubMedCentral
79.
Ahmad A, Menezes J. Binding of the Epstein-Barr virus to human platelets causes the release of transforming growth factor-beta. J Immunol. 1997;159(8):3984–8.PubMed
Metadata
Title
Human blood platelets and viruses: defense mechanism and role in the removal of viral pathogens
Authors
Masresha Seyoum
Bamlaku Enawgaw
Mulugeta Melku
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2018
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-018-0170-8

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