Abstract
BackgroundDengue Virus (DENV) is the most common mosquito-borne viral infection worldwide. Important target cells during DENV infection are macrophages, monocytes, and immature dendritic cells (imDCs). DENV-infected cells are known to secrete a large number of partially immature and fully immature particles alongside mature virions. Fully immature DENV particles are considered non-infectious, but antibodies have been shown to rescue their infectious properties. This suggests that immature DENV particles only contribute to the viral load observed in patients with a heterologous DENV re-infection.Methodology/Principal findingsIn this study, we re-evaluated the infectious properties of fully immature particles in absence and presence of anti-DENV human serum. We show that immature DENV is infectious in cells expressing DC-SIGN. Furthermore, we demonstrate that immature dendritic cells, in contrast to macrophage-like cells, do not support antibody-dependent enhancement of immature DENV.Conclusions/SignificanceOur data shows that immature DENV can infect imDCs through interaction with DC-SIGN, suggesting that immature and partially immature DENV particles may contribute to dengue pathogenesis during primary infection. Furthermore, since antibodies do not further stimulate DENV infectivity on imDCs we propose that macrophages/monocytes rather than imDCs contribute to the increased viral load observed during severe heterotypic DENV re-infections.
Highlights
Dengue virus (DENV), a flavivirus within the Flaviviridae family, is the most common mosquito-borne viral infectious agent worldwide
We showed before that LoVo-derived Dengue Virus (DENV) has an average precursor membrane (prM) content of 9469%, demonstrating that LoVo-derived DENV is fully immature [11].The prM protein is known to control viral infectivity [11,14,18,20,21], and we observed before that the specific infectivity of LoVo-derived DENV is at least 10,000 fold reduced compared to that of std DENV generated in C6/36 cells [11,17,32]
The specific infectivity of the immature DENV-2 batch used in this study was,100,000 fold reduced compared to that of std DENV-2, again demonstrating that immature DENV-2 is essentially non-infectious in BHK-2115 cells
Summary
Dengue virus (DENV), a flavivirus within the Flaviviridae family, is the most common mosquito-borne viral infectious agent worldwide. In ADE, pre-existing cross-reactive antibodies are hypothesized to bind to the newly infecting virus and facilitate efficient replication in Fcy-receptor-expressing cells, thereby increasing the infected cell mass and viral load. A high viral load is often a prelude for severe disease development [7]. Dengue Virus (DENV) is the most common mosquito-borne viral infection worldwide. Immature DENV particles are considered non-infectious, but antibodies have been shown to rescue their infectious properties. This suggests that immature DENV particles only contribute to the viral load observed in patients with a heterologous DENV re-infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
