title: Complement protein C1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner.
abstract: Severe dengue virus infection can occur in humans with pre-existing antibodies against the virus. This observation led to the hypothesis that a subneutralizing antibody level in vivo can increase viral burden and cause more severe disease. Indeed, antibody-dependent enhancement of infection (ADE) in vitro has been described for multiple viruses, including the flaviviruses dengue virus and West Nile virus. Here, we demonstrate that the complement component C1q restricts ADE by anti-flavivirus IgG antibodies in an IgG subclass-specific manner in cell culture and in mice. IgG subclasses that avidly bind C1q induced minimal ADE in the presence of C1q. These findings add a layer of complexity for the analysis of humoral immunity and flavivirus infection.
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Erin
authors: E
authors: Mehlhop
authors: Camilo
authors: C
authors: Ansarah-Sobrinho
authors: Syd
authors: S
authors: Johnson
authors: Michael
authors: M
authors: Engle
authors: Daved H
authors: DH
authors: Fremont
authors: Theodore C
authors: TC
authors: Pierson
authors: Michael S
authors: MS
authors: Diamond
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D015922:Complement C1q / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology* / Q000472:pathogenicity; D018177:Flavivirus Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D015922:Complement C1q