Immature dengue virus: a veiled pathogen?
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.
Rodenhuis-Zybert
Izabela A
IA
Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
van der Schaar
Hilde M
HM
da Silva Voorham
Júlia M
JM
van der Ende-Metselaar
Heidi
H
Lei
Huan-Yao
HY
Wilschut
Jan
J
Smit
Jolanda M
JM
D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D003715:Dengue / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity*; D045683:Furin / Q000378:metabolism*; D006801:Humans; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014771:Virion / Q000276:immunology*
D000914:Antibodies, Viral; C445323:FCGR2A protein, human; D017452:Receptors, IgG; D045683:Furin