Skip to main content
. 2011 Dec 13;2(6):e00276-11. doi: 10.1128/mBio.00276-11

FIG 1 .

FIG 1

Neutralization of insect cell- and mammalian cell-derived DENV-2 by mouse serum is mediated by the lectin pathway. (A and C) Neutralization of C6/36 cell-derived (A) or Vero cell-derived (C) DENV-2 in the presence of 10% (vol/vol) complement-deficient serum. DENV was incubated with naïve serum from wild-type (WT) mice or complement-deficient (MBL-A−/− × MBL-C−/− [MBL A/C−/−] MASP2−/−, C1q−/−, C4−/−, C3−/−, C3−/− × C4−/− [C3/C4] DKO, C5−/−, fB−/−, or fD−/−) or antibody-deficient (RAG1−/−) mice prior to addition to a monolayer of BHK21-15 cells. Infectivity was determined 4 days later by plaque assay. Data are presented as the percent neutralization by a given complement-deficient or antibody-deficient serum compared to wild-type C57BL/6 serum. Error bars indicate standard errors of the means (SEM) for up to 6 independent experiments with each condition performed in duplicate. Values that are significantly different from the value for wild-type C57BL/6 serum are indicated by asterisks as follows: *, P < 0.05; **, P < 0.01; ***, P < 0.001. (B and D) Serum neutralization of C6/36 cell-derived (B) or Vero cell-derived (D) DENV is abolished in the presence of mannan. DENV was preincubated with an increasing percentage of wild-type serum in the presence or absence of mannan (100 µg/ml). The percentage of neutralization was calculated based on reduction of the number of plaques for a given condition compared to heat-inactivated (HI) wild-type serum. Error bars indicate SEM from 3 independent experiments performed in duplicate. Values that are significantly different from the value for the wild type are indicated by asterisks and brackets as follows: *, P < 0.05; **, P < 0.01; ***, P < 0.001. (E) Model of DENV neutralization by complement. MBL binding to the virion surface initiates lectin pathway activation resulting in deposition of C4b and C3b. Binding of MBL also activates MASPs that directly cleave C3 without activation of C4 and C2 (the C4 and C2 bypass pathway). The alternative pathway amplification loop serves to generate more C3b deposition on the virus.