第9回千葉県胆膵研究会 11.

Additional file 13: Table S5. Statistical analysis of all experiments separated for transmission pairs with high and low diversity transmitters and for transmission pairs where recipient is closer to ancestral genotype, respectively

Simultaneous fit of the reaction constants and the stoichiometric parameters.

<p>Each panel shows the kinetic neutralisation curve (as predicted by <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002900#pcbi.1002900.e102" target="_blank">equation 6</a>) that best fitted kinetic neutralisation data. This data was extracted from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002900#pcbi.1002900-McLain1" target="_blank">[5]</a> where three monoclonal rat antibodies against HIV-1 IIIB were tested: (A) ICR39.3b (B) ICR39.13g (C) ICR41.1i. The estimated parameters for each best fit are summarised in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002900#pcbi-1002900-t002" target="_blank">table 2</a>.</p

Kinetic neutralisation curves for different spike number distributions.

<p>Binding constants are all , dissociation constants are all , the stoichiometry of entry is and the stoichiometry of trimer neutralisation is . Red curves have a spike number distribution with mean 10, where all virions in the case of the dashed line have exactly 10 spikes and in case of the dotted lines have an equal probability to have 2,3…, 18 spikes. The black curve underlies the HIV specific discretised Beta distribution with mean 14 and variance 49. The spike number distributions for the blue curves have mean 36, where the one for the dashed line has only virions expressing 36 spikes and the dotted line has 0–72 spikes.</p

Predictions for kinetic neutralisation curves for the elementary reaction model.

<p>(A) All binding constants are and all dissociation constants are . The stoichiometry of entry is assumed to be . The starting concentration of antibodies is and the starting concentration of trimers is . (B) Same constants as in (A) but the starting concentration of antibodies is . (C) The binding constants are and the dissociation constants are all . The stoichiometry of entry is and the antibody starting concentration is .</p

Parameter definitions.

<p>Parameter definitions.</p

Estimated parameters.

<p>Estimated parameters.</p

Influence of reaction parameters on the feasibility of estimating the stoichiometry of neutralisation,

<p><b>.</b> The concentration of spikes and antibodies is the same for all graphs, i.e. and and the stoichiometry of entry is . (A) All binding constants have the same value and all dissociation have the same value . (B) Same coloured graphs correspond to the same reaction constants. Blue curves: the -complex is built preferentially, due to the reaction constants . Red curves: the -complex is built preferentially, . Green curves: the -complexes are built preferentially, . (C) The binding constants decrease and the dissociation constants increase, i.e. . Only in this case are the kinetic neutralisation curves for different stoichiometries of neutralisation distinguishable.</p

Predictions for the relative infectivity for

<p><b>.</b> (A) The relative infectivity is shown as a function of the fractions of envelope proteins defective of function A, , and the fraction of envelope proteins defective of function B, . The grey plane shows the predictions for a model in which the two functional units A and B are located on the same envelope protein, the blue plane the model in which these function can be located on different envelope proteins. (B) The difference between the two models is the highest, if the fraction of one mutant is fixed at 0.265. (C) The relative infectivity for an experimental system in which the fraction of one mutant is fixed at maximum distinguishability and the fraction of the other mutant envelope protein is varied.</p

Relative infectivity curves for the best estimate of the stoichiometry of neutralization in the different models.

<p>The imperfect transfection model and the segregation model are omitted due to the lack of reliability of the estimates. In the other models, the best fit is obtained for . The entry parameters are included from the estimation of the entry parameters in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000713#pcbi.1000713-Magnus1" target="_blank">[1]</a>: for the basic model, for the proximity model and for the soft threshold model.</p

Dependence of the stoichiometry of neutralization, , on the trimer's infectiousness.

<p>Wild-type envelope proteins are colored black, mutant envelope proteins red and antibodies green. Due to saturation with antibodies prior to the infectivity experiments, all wild-type envelope proteins are assumed to be bound. Functional trimers are marked with “+”, non-functional ones with “−”.</p