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. 2015 Sep 2;89(22):11294–11311. doi: 10.1128/JVI.00946-15

FIG 4.

FIG 4

Similar to T-tropic viruses, M-tropic viruses are generally resistant to neutralization by non-CD4bs-targeting antibodies with subtle trends toward increased resistance to V1/V2-targeting antibodies and decreased resistance to a glycan-targeting antibody. Pseudotyped reporter viruses were exposed to various concentrations of the following in a TZM-bl neutralization assay: polyclonal sera from five HIV-infected subjects (a); purified polyclonal HIV-Ig (b); anti-V1/V2 MAbs PG9 (c), PG16 (d), and CH01 (e); antiglycosylation MAb 2G12 (f); anti-MPER MAbs 2F5 (g), and 4E10 (h); and anti-CD4i MAbs 17b (i) and 447-52D (j). The data for the acute and chronic infection subtype C viruses are reproduced from Ping et al. (3) to allow a comparison to a large data set of typical viral Env proteins. IC50s were calculated from dose-response curves and plotted. Dashed lines represent the limits of detection. IC50s above the limit of detection (LOD) were plotted at the LOD, except for pairs where both viruses had IC50s that exceeded the LOD, in which case the symbols were stacked above the LOD line. Data for the same Env-pseudotyped viruses were used in each panel: T-tropic acute (A) and chronic (C) infection viruses (black asterisks; panels b to h only), T-tropic viruses (T; closed symbols), and M-tropic viruses (M; open symbols). Subject-matched viruses are linked, and the IC50s of T-tropic and M-tropic viruses were compared using a Wilcoxon matched-pair test. M-tropic and subject-matched T-tropic Env proteins were not significantly different in neutralization by polyclonal sera (FANOVA = 0.8 [where ANOVA is analysis of variance], r2 = 0.1, P value = 0.6) (a) or HIV-Ig (Wpaired = 12, P value = 0.5) (b) or by MPER-targeting MAbs 2F5 (Wpaired = 1, P value = 1) (g) and 4E10 (Wpaired = −2, P value = 0.9) (h). M-tropic Env proteins trended toward increased resistance to neutralization by V1/V2-targeting MAbs PG9 (Wpaired = −13, P value = 0.1) (c), PG16 (Wpaired = −13, P value = 0.2) (d), and CH01 (Wpaired = −10, P value = 0.1) (e) and increased sensitivity to neutralization by glycosylation-targeting MAb 2G12 (Wpaired = 10, P value = 0.1) (h) compared to subject-matched T-tropic Env proteins. Thirteen of the 14 viruses were resistant to neutralization by MAbs 17b (i) and 447-52D (j), which target epitopes typically present only in the CD4-bound conformation of the viral Env protein from primary isolates (for 17b, Wpaired = 1, P value = 1; for 447-52D, Wpaired = 6, P value = 0.3).