Hepatitis C Virus Infected Human Megakaryocytes and Platelets: Intra- and Extracellular Evaluation
Keywords:
viral infection, megakaryocytes, platelets, hepatitis C virus, chronic hepatitis C
Abstract
This study aimed to determine whether the hepatitis C virus (HCV) infects human megakaryocytes and platelets and to measure the expression of receptors involved in virus-cell interaction. Platelets from healthy donors were infected with HCV in vitro and analyzed for viral expression and the receptors claudin-1 and cluster of differentiation 81 (CD81). HCV was detected on the surface and cytoplasm of both cells; cytoplasmic expression was higher compared to the surface. Platelets presented a claudin-1+/CD81-phenotype, and megakaryocytes showed aclaudin-1+/CD81+ phenotype. We conclude that megakaryocytes and platelets are susceptible to HCV infection, regardless of CD81 expression, and megakaryocytes may serve as possible sites of viral replication.
Downloads
How to Cite
References
Julie Sheldon, Nathan Beach, Elena Moreno, Isabel Gallego, David Piñeiro, Encarnación Martínez-Salas, Josep Gregori, Josep Quer, Juan Esteban, Charles Rice, Esteban Domingo, Celia Perales (2014) Increased Replicative Fitness Can Lead to Decreased Drug Sensitivity of Hepatitis C Virus. 88(20), 12098-12111.
X Li, L Jeffers, C Garon, E Fischer, J Scheffel, B Moore, K Reddy, M Demedina, E Schiff (1999) Persistence of hepatitis C virus in a human megakaryoblastic leukaemia cell line. 6(2), 107-114.
W Organization, Hepatitis, Virus (2023) Hepatitis C virus (HCV) fact sheet.
Nicola Fletcher, Garrick Wilson, Jacinta Murray, Ke Hu, Andrew Lewis, Gary Reynolds, Zania Stamataki, Luke Meredith, Ian Rowe, Guangxiang Luo, Miguel Lopez-ramirez, Thomas Baumert, Babette Weksler, Pierre-olivier Couraud, Kwang Kim, Ignacio Romero, Catherine Jopling, Susan Morgello, Peter Balfe, Jane Mckeating (2012) Hepatitis C Virus Infects the Endothelial Cells of the Blood-Brain Barrier. 142(3), 634-643.e6.
Giovanna Russelli, Paola Pizzillo, Gioacchin Iannolo, Floriana Barbera, Fabio Tuzzolino, Rosa Liotta, Mario Traina, Giovanni Vizzini, Bruno Gridelli, Ester Badami, Pier Conaldi (2017) HCV replication in gastrointestinal mucosa: Potential extra-hepatic viral reservoir and possible role in HCV infection recurrence after liver transplantation. 12(7), e0181683.
M Granato, C Zompetta, E Vescarelli, C Rizzello, A Cardi, S Valia, G Antonelli, C Marchese, M Torrisi, A Faggioni, M Cirone (2016) HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2. 6(1), 30649.
H Muller, E Pfaff, T Goeser, B Kallinowski, C Solbach, L Theilmann (1993) Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication. 74(4), 669-676.
Maria‐cristina Navas, Anne Fuchs, Evelyne Schvoerer, Alain Bohbot, Anne‐marie Aubertin, Françoise Stoll‐keller (2002) Dendritic cell susceptibility to hepatitis C virus genotype 1 infection. 67(2), 152-161.
R Wang, P Bare, V De Giorgi, K Matsuura, K Salam, T Grandinetti, C Schechterly, H Alter, I Castillo, E Rodríguez-Iñigo, J Bartolomé, S De Lucas, N Ortíz-Movilla, J López-Alcorocho, M Pardo, V Carreño (2005) Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection. 54, 682-685.
T Chang, K Young, Y Yang, H Lei, H Wu (1996) Hepatitis C virus RNA in peripheral blood mononuclear cells: Comparing acute and chronic hepatitis C virus infection. 23, 977-981.
K Salam, R Wang, T Grandinetti, V De Giorgi, H Alter, R Allison (2018) Binding of Free and Immune Complex-Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System. 68, 2118-2129.
Yasuteru Kondo, T Shimosegawa (2013) Direct effects of hepatitis C virus on the lymphoid cells. 19(44), 7889.
Juliana Padovani, Silvia Corvino, Jan Drexler, Giovanni Silva, Maria Pardini, Rejane Grotto (2013) In vitro detection of hepatitis C virus in platelets from uninfected individuals exposed to the virus. 46(2), 154-155.
H Lerat, M ; Trabaud, O Vidalin, M Major, C; Trépo, G Inchauspé (1996) Specificdetectionofhepatitis C virusminusstrand RNA in hematopoieticcells. 97, 845-851.
Mayla Hsu, Jie Zhang, Mike Flint, Carine Logvinoff, Cecilia Cheng-Mayer, Charles Rice, Jane Mckeating (2003) Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. 100(12), 7271-7276.
Adilson De Almeida, Marilza Campos-De-Magalhães, Olívia De Melo Marçal, Carlos Brandão-Mello, Margareti Okawa, Rosane De Oliveira, Márcia Do Espírito-Santo, Clara Yoshida, Elisabeth Lampe (2004) Hepatitis C virus-associated thrombocytopenia: a controlled prospective, virological study. 83(7), 434-440.
Sumit Dahal, Smrity Upadhyay, Rashmi Banjade, Prajwal Dhakal, Navin Khanal, Vijaya Bhatt (2017) THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION. 9(1), e2017019.
S Kedia, V Bhatt, S Rajan, P Tandra, R El Behery, M Akhtari (2014) Hematological and Musculoskeletal Manifestations of Systemic Lupus Erythematosus in A Patient with Chronic Hepatitis C Virus Infection. 8(3), 179-S192.
Howard Liebman (2008) Viral-Associated Immune Thrombocytopenic Purpura. 2008(1), 212-218.
Massimo Franchini, Dino Veneri, Giuseppe Lippi (2017) Thrombocytopenia and infections. 10(1), 99-106.
Shojiro Ichimata, Mikiko Kobayashi, Kohei Honda, Soichiro Shibata, Akihiro Matsumoto, Hiroyuki Kanno (2017) Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection. 23(35), 6540-6545.
J Ariede, M Pardini, G Silva, R Grotto (2015) Platelets can be a biological compartment for the Hepatitis C Virus. 46, 627-629.
Samir Hamaia, Chengyao Li, Jean-Pierre Allain (2001) The dynamics of hepatitis C virus binding to platelets and 2 mononuclear cell lines. 98(8), 2293-2300.
G Bordin, M Ballaré, P Zigrossi, M Bertoncelli, L Paccagnino, A Baroli, M Brambilla, A Monteverde, E Inglese (1995) A laboratory and thrombokinetic study of HCV-associated thrombocytopenia: a direct role of HCV in bone marrow exhaustion?. 13(Suppl 13), 39-43.
A Tomer, P Friese, R Conklin, W Bales, L Archer, L Harker, S Burstein (1989) Flow cytometric analysis of megakaryocytes from patients with abnormal platelet counts. 74(2), 594-601.
T Ishibashi, Z Ruggeri, L Harker, S Burstein (1986) Separation of human megakaryocytes by state of differentiation on continuous gradients of Percoll: size and ploidy analysis of cells identified by monoclonal antibody to glycoprotein IIb/IIIa. 67(5), 1286-1292.
Robert Liwski, Anna Greenshields, David Conrad, Cathi Murphey, Robert Bray, Jorge Neumann, Howard Gebel (2009) Rapid optimized flow cytometric crossmatch (FCXM) assays: The Halifax and Halifaster protocols. 79(1), 28-38.
A Roder, C Vazquez, S Horner (2019) The acidic domain of the hepatitis C virus NS4A protein is required for viral assembly and envelopment through interactions with the viral E1 glycoprotein. 15, 1007163.
Fabrice Cognasse, Hind Hamzeh, Patricia Chavarin, Sophie Acquart, Christian Genin, Olivier Garraud (2005) Evidence of Toll‐like receptor molecules on human platelets. 83(2), 196-198.
Sergey Shiryaev, Elliot Thomsen, Piotr Cieplak, Eugene Chudin, Anton Cheltsov, Mark Chee, Igor Kozlov, Alex Strongin (2012) New Details of HCV NS3/4A Proteinase Functionality Revealed by a High-Throughput Cleavage Assay. 7(4), e35759.
Yong-Zhe Zhu, X Qian, P Zhao, Z Qi (2014) How hepatitis C virus invades hepatocytes: The mystery of viral entry. 20(13), 3457.
L Fénéant, S Levy, L Cocquerel (2014) CD81 and hepatitis C virus (HCV) infection. 6, 535-572.
Selma Dahmane, Eric Rubinstein, Pierre-Emmanuel Milhiet (2014) Viruses and Tetraspanins: Lessons from Single Molecule Approaches. 6(5), 1992-2011.
A Manzin, M Candela, S Paolucci, M Caniglia, A Gabrielli, M Clementi (1994) Presence of hepatitis C virus (HCV) genomic RNA and viral replicative intermediates in bone marrow and peripheral blood mononuclear cells from HCV-infected patients. 1(2), 160-163.
Marek Radkowski, Joanna Kubicka, Elzbieta Kisiel, Janusz Cianciara, Marek Nowicki, Jorge Rakela, Tomasz Laskus (2000) Detection of active hepatitis C virus and hepatitis G virus/GB virus C replication in bone marrow in human subjects. 95(12), 3986-3989.
Astrid Zahn, Nicola Jennings, Willem Ouwehand, Jean-Pierre Allain (2006) Hepatitis C virus interacts with human platelet glycoprotein VI. 87(8), 2243-2251.
Noha Hassuna, Peter Monk, Gregory Moseley, Lynda Partridge (2009) Strategies for Targeting Tetraspanin Proteins. 23(6), 341-359.
Stephen Fitter, Paul Sincock, Corina Jolliffe, Leonie Ashman (1999) Transmembrane 4 superfamily protein CD151 (PETA-3) associates with β1 and αIIbβ3 integrins in haemopoietic cell lines and modulates cell-cell adhesion. 338(1), 61-70.
C Boucheix, E Rubinstein (2001) Tetraspanins. 58(9), 1189-1205.
A Abou El Azm, H El-Bate, L Abo-Ali, N Mansour, H Ghoraba, M Salem (2012) Correlation of viral load with bone marrow and hematological changes in pale patients with chronic hepatitis C virus. 157, 1579-1586.
Magdy El Barbary, Alaa Saad, Fadia Attia, Magda Mandour, Mohamed Haidara, Mohammad Dallak, Esma Isenovic (2010) Thrombocytopenia in Patients With Chronic Hepatitis C: A Possible Role of HCV on Platelet Progenitor Cell Maturation. 61(3), 304-313.
N Afdhal, J Mchutchison (2007) Review article: pharmacological approaches for the treatment of thrombocytopenia in patients with chronic liver disease and hepatitis C infection. 26(s1), 29-39.
Alice Assinger (2014) Platelets and Infection â€" An Emerging Role of Platelets in Viral Infection. 5.
Yong-Zhe Zhu, Yuan Luo, Ming-Mei Cao, Yuan Liu, Xiao-Qing Liu, Wen Wang, Da-Ge Wu, Mo Guan, Qing-Qiang Xu, Hao Ren, Ping Zhao, Zhong-Tian Qi (2012) Significance of palmitoylation of CD81 on its association with tetraspanin-enriched microdomains and mediating hepatitis C virus cell entry. 429(2), 112-123.
R Tawar, C Colpitts, J Lupberger, H El-Saghire, M Zeisel, T Baumert (2015) Claudins and pathogenesis of viral infection. 42, 39-46.
Quentin Sattentau (2008) Avoiding the void: cell-to-cell spread of human viruses. 6(11), 815-826.
Camila Verdichio‐moraes, Cecília Toralles‐pereira, Rejane Grotto, Giovanni Silva, Maria Pardini (2009) Allelic frequencies of HPA‐1 to 5 human platelet antigens in patients infected with hepatitis C virus. 81(4), 757-759.
Galit Alter, Jessica Malenfant, Marcus Altfeld (2004) CD107a as a functional marker for the identification of natural killer cell activity. 294(1-2), 15-22.
Ágnes Holczbauer, Benedek Gyöngyösi, Gábor Lotz, Péter Törzsök, Pál Kaposi-Novák, Attila Szijártó, Péter Tátrai, Péter Kupcsulik, Zsuzsa Schaff, András Kiss (2014) Increased Expression of Claudin-1 and Claudin-7 in Liver Cirrhosis and Hepatocellular Carcinoma. 20(3), 493-502.
Jesús Torres-Flores, Carlos Arias (2015) Tight Junctions Go Viral!. 7(9), 5145-5154.
Virgínia Gondar, Francisca Molina-Jiménez, Takayuki Hishiki, Luisa García-Buey, George Koutsoudakis, Kunitada Shimotohno, Ignacio Benedicto, Pedro Majano (2015) Apolipoprotein E, but Not Apolipoprotein B, Is Essential for Efficient Cell-to-Cell Transmission of Hepatitis C Virus. 89(19), 9962-9973.
J Witteveldt, M Evans, J Bitzegeio, G Koutsoudakis, A Owsianka, A Angus, Z-Y Keck, S Foung, T Pietschmann, C Rice, A Patel (2009) CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. 90(1), 48-58.
Isabel Fofana, Samira Fafi-kremer, Patric Carolla, Catherine Fauvelle, Muhammad Zahid, Marine Turek, Laura Heydmann, Karine Cury, Juliette Hayer, Christophe Combet, François-loïc Cosset, Thomas Pietschmann, Marie-sophie Hiet, Ralf Bartenschlager, François Habersetzer, Michel Doffoël, Zhen-yong Keck, Steven Foung, Mirjam Zeisel, Françoise Stoll-keller, Thomas Baumert (2012) Mutations That Alter Use of Hepatitis C Virus Cell Entry Factors Mediate Escape From Neutralizing Antibodies. 143(1), 223-233.e9.
Frederik Graw, Danyelle Martin, Alan Perelson, Susan Uprichard, Harel Dahari (2015) Quantification of Hepatitis C Virus Cell-to-Cell Spread Using a Stochastic Modeling Approach. 89(13), 6551-6561.
Huahao Fan, Luhua Qiao, Kyung-Don Kang, Junfen Fan, Wensheng Wei, Guangxiang Luo (2017) Attachment and Postattachment Receptors Important for Hepatitis C Virus Infection and Cell-to-Cell Transmission. 91(13), 280-297.
Birke Bartosch, Jean Dubuisson (2010) Recent Advances in Hepatitis C Virus Cell Entry. 2(3), 692-709.
Published
2025-01-09
Issue
Section
License
Copyright (c) 2024 Authors and Global Journals Private Limited

This work is licensed under a Creative Commons Attribution 4.0 International License.