Dengue and the Lectin Pathway of the Complement System
Open Access
- 24 June 2021
- Vol. 13 (7), 1219
- https://doi.org/10.3390/v13071219
Abstract
Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system’s lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern recognition receptor (PRR) binding efficiency. The important PRR, mannan binding lectin (MBL), mediates DENV neutralization through (1) a complement activation-independent mechanism via direct MBL glycan recognition, thereby inhibiting DENV attachment to host target cells, or (2) a complement activation-dependent mechanism following the attachment of complement opsonins C3b and C4b to virion surfaces. The serum concentrations of lectin PRRs and their polymorphisms influence these LP activities. Conversely, to escape the LP attack and enhance the infectivity, DENV utilizes the secreted form of nonstructural protein 1 (sNS1) to counteract the MBL effects, thereby increasing viral survival and dissemination.Keywords
Funding Information
- Faculty of Medicine Siriraj Hospital, Mahidol University (R016010008 and R016234004)
- Mahidol University (Not applicable)
- National Science and Technology Development Agency (P-15-51429)
- National Institutes of Health (R35-GM136352-01)
This publication has 118 references indexed in Scilit:
- Lectin Switching During Dengue Virus InfectionThe Journal of Infectious Diseases, 2011
- The lectin pathway of complement activation contributes to protection from West Nile virus infectionVirology, 2011
- Immunodominant T-cell responses to dengue virus NS3 are associated with DHFProceedings of the National Academy of Sciences of the United States of America, 2010
- Direct Complement Restriction of Flavivirus Infection Requires Glycan Recognition by Mannose-Binding LectinCell Host & Microbe, 2010
- Antagonism of the complement component C4 by flavivirus nonstructural protein NS1The Journal of Experimental Medicine, 2010
- Structural proteomics of dengue virusCurrent Opinion in Microbiology, 2008
- DengueThe Lancet, 2007
- Protective immune responses against West Nile virus are primed by distinct complement activation pathwaysThe Journal of Experimental Medicine, 2006
- Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic feverNature Medicine, 2003
- DC-SIGN (CD209) Mediates Dengue Virus Infection of Human Dendritic CellsThe Journal of Experimental Medicine, 2003