Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

PLoS Pathogens

Lucy Reynell¹  Irene A. Abela¹  Huldrych F. Günthard¹  Alexandra Trkola¹  Merle Schanz²  Livia Berlinger³  Peter Rusert³ 

[1] Institute of Medical Virology, University of Zurich, Zurich, Switzerland;MD-PhD Program, University of Zurich, Zurich, Switzerland;PhD Program in Microbiology and Immunology, University of Zurich, Zurich, Switzerland

关键词: Antibodies;    HIV;    Luciferase;    Cell fusion;    Viral replication;    Virions;    Viral transmission;    infection;    T cells;   

DOI  :  10.1371/journal.ppat.1002634

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo.

【 授权许可】

CC BY