Immature Dengue Virus: A Veiled Pathogen?
Izabela A. Rodenhuis-Zybert,Hilde M. van der Schaar,Júlia M. da Silva Voorham,Heidi van der Ende-Metselaar,Huan Yao Lei,Jan Wilschut,Jolanda M. Smit +6 more
TLDR
It is demonstrated that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells and enzymatic activity of furin is critical to render the internalized immature virus infectious.Abstract:
Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease.read more
Citations
More filters
Journal ArticleDOI
Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis
Jean K. Millet,Gary R. Whittaker +1 more
TL;DR: This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.
Journal ArticleDOI
The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity
Martina Beltramello,Katherine L. Williams,Cameron P. Simmons,Annalisa Macagno,Luca Simonelli,Nguyen Than Ha Quyen,Soila Sukupolvi-Petty,Erika Navarro-Sanchez,Paul R. Young,Aravinda M. de Silva,Félix A. Rey,Luca Varani,Stephen S. Whitehead,Michael S. Diamond,Eva Harris,Antonio Lanzavecchia,Federica Sallusto +16 more
TL;DR: These findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.
Journal ArticleDOI
Dengue virus life cycle: viral and host factors modulating infectivity
TL;DR: An overview of the infectious life cycle of DENV is given and the viral and host factors that are important in controlling DENV infection are discussed.
Journal ArticleDOI
The Human Antibody Response to Dengue Virus Infection
TL;DR: These studies establish that human and mouse antibodies recognize distinct epitopes on the dengue virion, and indicate that antibody neutralization of DENVs is a “multi-hit” phenomenon that requires the binding of multiple antibodies to neutralize a virion.
Journal ArticleDOI
Dengue viruses - an overview.
TL;DR: A fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence in dengue viruses.
References
More filters
Journal ArticleDOI
Pathogenesis of dengue: challenges to molecular biology
TL;DR: This work has identified a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome, in Southeast Asian children, which recently has also been identified in children infected with the virus in Puerto Rico.
Journal ArticleDOI
Dengue Viremia Titer, Antibody Response Pattern, and Virus Serotype Correlate with Disease Severity
David W. Vaughn,Sharone Green,Siripen Kalayanarooj,Bruce L. Innis,Suchitra Nimmannitya,Saroj Suntayakorn,Timothy P. Endy,Boonyos Raengsakulrach,Alan L. Rothman,Francis A. Ennis,Ananda Nisalak +10 more
TL;DR: Higher peak titers were associated with increased disease severity for the 31 patients with a peak titer identified, and increased dengue disease severity correlated with high viremia titer, secondary d Dengue virus infection, and DEN-2 virus type.
Book ChapterDOI
Neutralization and antibody-dependent enhancement of dengue viruses.
TL;DR: This chapter highlights the neutralization and protection against dengue infection by antibodies and relevant clinical and epidemiological and experimental studies that support the phenomenon of antibody-dependent enhanced (ADE) are discussed.
Journal ArticleDOI
High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever
Daniel H. Libraty,Paul R. Young,Darren Pickering,Timothy P. Endy,Siripen Kalayanarooj,Sharone Green,David W. Vaughn,Ananda Nisalak,Francis A. Ennis,Alan L. Rothman +9 more
TL;DR: In this paper, the secreted dengue virus nonstructural protein NS1 (sNS1) was measured daily in 32 children with Dengue-2 virus infections participating in a prospective, hospital-based study.
Journal ArticleDOI
Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants.
TL;DR: The hypothesis that maternal dengue antibodies play a dual role by first protecting and later increasing the risk of development of d Dengue hemorrhagic fever/dengue shock syndrome in infants who become infected by denge 2 virus is consistent.
Related Papers (5)
Cross-Reacting Antibodies Enhance Dengue Virus Infection in Humans
Wanwisa Dejnirattisai,Amonrat Jumnainsong,Naruthai Onsirisakul,Naruthai Onsirisakul,Patricia Fitton,Sirijitt Vasanawathana,Wannee Limpitikul,Chunya Puttikhunt,Carolyn Edwards,Thaneeya Duangchinda,Sunpetchuda Supasa,Kriangkrai Chawansuntati,Prida Malasit,Prida Malasit,Juthathip Mongkolsapaya,Juthathip Mongkolsapaya,Gavin R. Screaton +16 more
The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity
Martina Beltramello,Katherine L. Williams,Cameron P. Simmons,Annalisa Macagno,Luca Simonelli,Nguyen Than Ha Quyen,Soila Sukupolvi-Petty,Erika Navarro-Sanchez,Paul R. Young,Aravinda M. de Silva,Félix A. Rey,Luca Varani,Stephen S. Whitehead,Michael S. Diamond,Eva Harris,Antonio Lanzavecchia,Federica Sallusto +16 more
The global distribution and burden of dengue
Samir Bhatt,Peter W. Gething,Oliver J. Brady,Jane P. Messina,Andrew Farlow,Catherine L. Moyes,John M. Drake,John M. Drake,John S. Brownstein,Anne G. Hoen,Osman Sankoh,Osman Sankoh,Monica F. Myers,Dylan B. George,Thomas Jaenisch,G. R. William Wint,Cameron P. Simmons,Thomas W. Scott,Thomas W. Scott,Jeremy Farrar,Jeremy Farrar,Simon I. Hay,Simon I. Hay +22 more