Complement protein C1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner.
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.
Mehlhop
Erin
E
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ansarah-Sobrinho
Camilo
C
Johnson
Syd
S
Engle
Michael
M
Fremont
Daved H
DH
Pierson
Theodore C
TC
Diamond
Michael S
MS
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
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D015922:Complement C1q