Published 6 issues per year
ISSN Print: 1040-8401
ISSN Online: 2162-6472
IF:
1.3
5-Year IF:
2.6
Eigenfactor:
0.00079
JCI:
0.24
SJR:
0.429
SNIP:
0.287
CiteScore™::
2.7
H-Index:
81
Indexed in
Emerging Concepts in Dengue Pathogenesis: Interplay between Plasmablasts, Platelets, and Complement in Triggering Vasculopathy
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ABSTRACT
Dengue is a mosquito-borne disease caused by infection with dengue virus (DENV) that represents a serious and expanding global health threat. Most DENV infections are inapparent or produce mild and self-limiting illness; however a significant proportion results in severe disease characterized by vasculopathy and plasma leakage that may culminate in shock and death. The cause of dengue-associated vasculopathy is likely to be multifactorial but remains essentially unknown. Severe disease is manifest during a critical phase from 4 to 7 days after onset of symptoms, once the virus has disappeared from the circulation but before the peak of T-cell activation, suggesting that other factors mediate vasculopathy. Here, we present evidence for a combined role of plasmablasts, complement, and platelets in driving severe disease in DENV infection. Massive expansion of virus-specific plasmablasts peaks during the critical phase of infection, coincident with activation of complement and activation and depletion of platelets. We propose a step-wise model in which virus-specific antibodies produced by plasmablasts form immune complexes, leading to activation of complement and release of vasoactive anaphylatoxins. Platelets become activated through binding of complement- and antibody-coated virus, as well as direct binding of virus to DC-SIGN, leading to the release of inflammatory microparticles and cytokines and sequestration of platelets in the microvasculature. We suggest that the combined effects of anaphylatoxins, inflammatory microparticles, and platelet sequestration serve as triggers of vasculopathy in severe dengue.
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Assinger Alice, Platelets and Infection – An Emerging Role of Platelets in Viral Infection, Frontiers in Immunology, 5, 2014. Crossref
-
Oehadian A., Michels M., de Mast Q., Prihatni D., Puspita M., Hartantri Y., Sinarta S., van der Ven A. J. A. M., Alisjahbana B., New parameters available on Sysmex XE-5000 hematology analyzers contribute to differentiating dengue from leptospirosis and enteric fever, International Journal of Laboratory Hematology, 37, 6, 2015. Crossref
-
Oliveira João Fernando Picollo, Burdmann Emmanuel A., Dengue-associated acute kidney injury, Clinical Kidney Journal, 8, 6, 2015. Crossref
-
Mao Song, Zhang Jianhua, Role of complement in glomerular diseases, Journal of Receptors and Signal Transduction, 36, 3, 2016. Crossref
-
Speth Cornelia, Rambach Günter, Würzner Reinhard, Lass-Flörl Cornelia, Kozarcanin Huda, Hamad Osama A., Nilsson Bo, Ekdahl Kristina N., Complement and platelets: Mutual interference in the immune network, Molecular Immunology, 67, 1, 2015. Crossref
-
Brasier Allan R., Zhao Yingxin, Wiktorowicz John E., Spratt Heidi M., Nascimento Eduardo J.M., Cordeiro Marli T., Soman Kizhake V., Ju Hyunsu, Recinos Adrian, Stafford Susan, Wu Zheng, Marques Ernesto T.A., Vasilakis Nikos, Molecular classification of outcomes from dengue virus -3 infections, Journal of Clinical Virology, 64, 2015. Crossref
-
Adibi Jennifer J, Marques Ernesto T A, Cartus Abigail, Beigi Richard H, Teratogenic effects of the Zika virus and the role of the placenta, The Lancet, 387, 10027, 2016. Crossref
-
Clarke Jennifer N., Davies Lorena K., Calvert Julie K., Gliddon Briony L., Shujari Wisam H. Al, Aloia Amanda L., Helbig Karla J., Beard Michael R., Pitson Stuart M., Carr Jillian M., Reduction in sphingosine kinase 1 influences the susceptibility to dengue virus infection by altering antiviral responses, Journal of General Virology, 97, 1, 2016. Crossref
-
Jeewandara Chandima, Gomes Laksiri, Wickramasinghe N., Gutowska-Owsiak Danuta, Waithe Dominic, Paranavitane S. A., Shyamali N. L. A., Ogg Graham S., Malavige Gathsaurie Neelika, de Silva Aravinda M, Platelet Activating Factor Contributes to Vascular Leak in Acute Dengue Infection, PLOS Neglected Tropical Diseases, 9, 2, 2015. Crossref
-
Fong I. W., Chikungunya Virus and Zika Virus Expansion: An Imitation of Dengue Virus, in Emerging Zoonoses, 2017. Crossref
-
Al-Shujairi Wisam H., Clarke Jennifer N., Davies Lorena T., Alsharifi Mohammed, Pitson Stuart M., Carr Jillian M., Jin Xia, Intracranial Injection of Dengue Virus Induces Interferon Stimulated Genes and CD8+ T Cell Infiltration by Sphingosine Kinase 1 Independent Pathways, PLOS ONE, 12, 1, 2017. Crossref
-
Hottz Eugenio D., Quirino-Teixeira Anna Cecíllia, Valls-de-Souza Rogério, Zimmerman Guy A., Bozza Fernando A., Bozza Patrícia T., Platelet function in HIV plus dengue coinfection associates with reduced inflammation and milder dengue illness, Scientific Reports, 9, 1, 2019. Crossref
-
Carr Jillian M., Cabezas‐Falcon Sheila, Dubowsky Joshua G., Hulme‐Jones Jarrod, Gordon David L., Dengue virus and the complement alternative pathway, FEBS Letters, 594, 16, 2020. Crossref
-
Aguilar-Briseño José A., Upasani Vinit, Ellen Bram M. ter, Moser Jill, Pauzuolis Mindaugas, Ruiz-Silva Mariana, Heng Sothy, Laurent Denis, Choeung Rithy, Dussart Philippe, Cantaert Tineke, Smit Jolanda M., Rodenhuis-Zybert Izabela A., TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis, Nature Communications, 11, 1, 2020. Crossref
-
Mallhi Tauqeer Hussain, Khan Yusra Habib, Adnan Azreen Syazril, Tanveer Nida, Aftab Raja Ahsan, Dengue-Induced Renal Complications, in Expanded Dengue Syndrome, 2021. Crossref
-
Siddiqui Zaki, Yadav Shyam Mohan, Nath Kshitiz, Rathor Gopambuj Singh, Prevalence of Itching in Dengue and Its Correlation with Thrombocytopenia in Bundelkhand Region- A Tertiary Care Hospital-Based Study in the Region of Central India, Journal of Evolution of Medical and Dental Sciences, 9, 13, 2020. Crossref
-
Lo Yu-Chih, Chien Yu-Wen, Perng Guey Chuen, Could inactivation of platelets be key to preventing thrombocytopenia in dengue virus infected patients?, Future Virology, 12, 7, 2017. Crossref
-
da Costa Rasinhas Arthur, Cunha Jácome Fernanda, Cardoso Caldas Gabriela, Teixeira de Almeida Ana Luisa, Nunes da Silva Marcos Alexandre, Dias Coutinho de Souza Daniel, Carlos Paulino Amanda, Mendes Bandeira Derick, Leonardo Raphael, Conrado Guerra Nunes Priscila, Mohana-Borges Ronaldo, Monika Barth Ortrud, Barreto dos Santos Flavia, Ferreira Barreto Vieira Debora, Morphological Aspects and Viremia Analysis of BALB/c Murine Model Experimentally Infected with Dengue Virus Serotype 4, Viruses, 13, 10, 2021. Crossref
-
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-
Schneider Christine A., Calvo Eric, Peterson Karin E., Arboviruses: How Saliva Impacts the Journey from Vector to Host, International Journal of Molecular Sciences, 22, 17, 2021. Crossref
-
Cabezas-Falcon Sheila, Norbury Aidan J., Hulme-Jones Jarrod, Klebe Sonja, Adamson Penelope, Rudd Penny A., Mahalingam Suresh, Ong Li-Ching, Alonso Sylvie, Gordon David L., Carr Jillian M., Changes in complement alternative pathway components, factor B and factor H during dengue virus infection in the AG129 mouse, Journal of General Virology , 102, 3, 2021. Crossref
-
Quirino-Teixeira Anna Cecíllia, Andrade Fernanda Brandi, Pinheiro Mariana Brandi Mendonça, Rozini Stephane Vicente, Hottz Eugenio Damaceno, Platelets in dengue infection: more than a numbers game, Platelets, 33, 2, 2022. Crossref
-
El-Bacha Tatiana, Struchiner Claudio J., Cordeiro Marli Tenorio, Almeida Fabio C. L., Marques Ernesto Torres, Da Poian Andrea T., Ou J.-H. J., 1 H Nuclear Magnetic Resonance Metabolomics of Plasma Unveils Liver Dysfunction in Dengue Patients , Journal of Virology, 90, 16, 2016. Crossref
-
Cabezas Sheila, Bracho Gustavo, Aloia Amanda L., Adamson Penelope J., Bonder Claudine S., Smith Justine R., Gordon David L., Carr Jillian M., Diamond Michael S., Dengue Virus Induces Increased Activity of the Complement Alternative Pathway in Infected Cells, Journal of Virology, 92, 14, 2018. Crossref
-
Losada Paula X., DeLaura Isabel, Narváez Carlos F., Dengue Virus and Platelets: From the Biology to the Clinic, Viral Immunology, 35, 5, 2022. Crossref
-
Thakura Manisha, Chauhan A, Jambunathan Prashant, Awasthid Shikha, K Thilagavathi, PREDICTIVE CORRELATION OF ADVERSE CLINICAL OUTCOMES WITH THROMBOCYTOPENIA IN DENGUE FEVER: A SINGLE CENTER EXPERIENCE, GLOBAL JOURNAL FOR RESEARCH ANALYSIS, 2022. Crossref
-
Yong Yean Kong, Wong Won Fen, Vignesh Ramachandran, Chattopadhyay Indranil, Velu Vijayakumar, Tan Hong Yien, Zhang Ying, Larsson Marie, Shankar Esaki M., Dengue Infection - Recent Advances in Disease Pathogenesis in the Era of COVID-19, Frontiers in Immunology, 13, 2022. Crossref
-
Iba Toshiaki, Levy Jerrold H., Levi Marcel, Viral-Induced Inflammatory Coagulation Disorders: Preparing for Another Epidemic, Thrombosis and Haemostasis, 122, 01, 2022. Crossref