TY - JOUR
T1 - Complement Protein C1q Inhibits Antibody-Dependent Enhancement of Flavivirus Infection in an IgG Subclass-Specific Manner
AU - Mehlhop, Erin
AU - Ansarah-Sobrinho, Camilo
AU - Johnson, Syd
AU - Engle, Michael
AU - Fremont, Daved H.
AU - Pierson, Theodore C C.
AU - Diamond, Michael S.
N1 - Funding Information:
The authors thank members of our laboratories for review of the manuscript; Qing Xu for technical assistance; J. Atkinson for critical suggestions; and S. Halstead, S. Yoksan, and the Pediatric Dengue Vaccine Initiative for providing the cord blood serum samples. The work was supported by the Pediatric Dengue Vaccine Initiative (M.S.D., D.H.F., and T.C.P.), the NIH (grants AI061373 [M.S.D.] and U54 AI057160 [Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research], and NIAID contract HHSN266200600013C [MacroGenics]), and the Intramural Research Program of NIAID, NIH. Please note that there is a potential duality of interest. One of the authors (S.J.) works for MacroGenics, a firm that has obtained a license from Washington University for clinical development of humanized E16 antibody. M.S.D. is a consultant for MacroGenics.
PY - 2007/12/13
Y1 - 2007/12/13
N2 - 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.
AB - 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.
KW - MICROBIO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=36749028784&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2007.09.015
DO - 10.1016/j.chom.2007.09.015
M3 - Article
C2 - 18078693
AN - SCOPUS:36749028784
SN - 1931-3128
VL - 2
SP - 417
EP - 426
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 6
ER -