Dengue and the Lectin Pathway of the Complement System

• Published in: Viruses Vol. 13; no. 7; p. 1219
• Main Authors: Kraivong, Romchat, Punyadee, Nuntaya, Liszewski, M Kathryn, Atkinson, John P, Avirutnan, Panisadee
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.06.2021; MDPI
• Subjects: Animals; Antibodies; Asymptomatic; Complement activation; Complement component C3b; Complement Pathway, Mannose-Binding Lectin; Cytokines; Dengue - immunology; Dengue - virology; Dengue fever; Dengue hemorrhagic fever; dengue shock syndrome; dengue virus; Dengue Virus - immunology; Dengue Virus - pathogenicity; flavivirus; Humans; Illnesses; Immune Evasion; Infections; Infectious diseases; Infectivity; lectin complement pathway; Lectins; Lymphocytes; Mannan; Mannose-binding lectin; Mannose-Binding Lectin - blood; Mannose-Binding Lectin - genetics; Mannose-Binding Lectin - immunology; Mannose-Binding Lectin - metabolism; N-glycans; Opsonins; Pathogenesis; Pathogens; Pattern recognition receptors; Polymorphism, Single Nucleotide; Polysaccharides; Polysaccharides - immunology; Polysaccharides - metabolism; Receptors, Pattern Recognition - blood; Receptors, Pattern Recognition - genetics; Receptors, Pattern Recognition - immunology; Receptors, Pattern Recognition - metabolism; Review; Roles; Serotypes; Severe Dengue - immunology; Severe Dengue - virology; Viral diseases; Viral infections; Viral Nonstructural Proteins - metabolism; Virions; Virulence; dengue hemorrhagic fever; dengue fever; dengue shock syndrome; dengue virus; nonstructural protein NS1; flavivirus; lectin complement pathway
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13071219

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.