Immature Dengue Virus: A Veiled Pathogen?

Izabela A. Rodenhuis-Zybert*, Hilde M. van der Schaar, Júlia Da Silva-Voorham, Heidi van der Ende-Metselaar, Huan-Yao Lei, Jan Wilschut, Jolanda M. Smit

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

188 Citaten (Scopus)
280 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Artikelnummer1000718
Aantal pagina's9
TijdschriftPLoS Pathogens
Volume6
Nummer van het tijdschrift1
Vroegere onlinedatum8-jan-2010
DOI's
StatusPublished - 8-jan-2010

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