Donor and recipient envs from heterosexual human immunodeficiency virus subtype C transmission pairs require high receptor levels for entry

Abstract

Compact, glycan-restricted envelope (Env) glycoproteins are selected during heterosexual transmission of subtype C HIV-1. Donor and recipient glycoproteins (Envs) from six transmission pairs were evaluated for entry into HeLa cells expressing different levels of CD4 and CCR5. Donor and recipient Envs demonstrated efficient entry into cells expressing high levels of CD4 and CCR5, and entry declined as CCR5 levels decreased. Infectivity for all Envs was severely impaired in cells expressing low levels of CD4, even at the highest CCR5 levels. In 5/6 pairs, there was no significant difference in efficiency of receptor utilization between the donor and recipient Envs in these HeLa-derived cell lines. Thus, HIV-1 transmission does not appear to select for viruses that can preferentially utilize low levels of entry receptors.

FIG. 1.

High-CD4-expressing cell lines. Panels present results from cells expressing high levels of CD4 with decreasing levels of CCR5 (JC-6 > JC-10 > HI-J). (A to C) Infectivity for donor (closed circles) and recipient (open triangles) Envs for each transmission pair (indicated on the x axis) were plotted as a percentage of infectivity in JC-53 cells, which express high levels of CD4 and CCR5. Each symbol represents the mean of the results for three independent experiments performed in duplicate. The horizontal line for each set indicates the median with the interquartile range. (D to F) All donor and all recipient Envs were combined and plotted as in panels A to C. A horizontal line represents the median for each group. Controls for all panels included results from two NL4-3 Env clones, two BA-L clones, and one CCR5-dependent control Env clone, R14.11. The range of V1-V4 loop lengths for each donor:recipient pair was as follows: ZM53, 269 to 292:268; ZM109, 265 to 286:266; ZM135, 285 to 290:278; ZM153, 269 to 283:278; ZM205, 265 to 284:277; ZM215, 285 to 308:288.

FIG. 2.

Low-CD4-expressing cells. Panels present results from cells expressing decreasing levels of CCR5 (RC-49 > RC-55 > RC-30 > HI-R). Experiments are plotted as described in the legend for Fig. 1. A star indicates statistical significant difference (P < 0.05) between the medians of the donor and recipient Envs.