Journal article

CD4-and Time-Dependent Susceptibility of HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity

Wen Shi Lee, Jeremie Prevost, Jonathan Richard, Renee M van der Sluis, Sharon R Lewin, Marzena Pazgier, Andres Finzi, Matthew S Parsons, Stephen J Kent

JOURNAL OF VIROLOGY | AMER SOC MICROBIOLOGY | Published : 2019

Abstract

HIV-1-specific antibody-dependent cellular cytotoxicity (ADCC) antibodies within HIV-1-positive (HIV-1+) individuals predominantly target CD4-induced (CD4i) epitopes on HIV-1 envelope glycoprotein (Env). These CD4i epitopes are usually concealed on the surface of infected cells due to CD4 downregulation by the HIV-1 accessory proteins Nef and Vpu. We hypothesized that early-stage infected cells in the process of downregulating CD4 could be more susceptible to ADCC than late-stage infected cells that have fully downregulated CD4. There was significantly higher binding of antibodies within plasma from HIV-1-infected individuals to early-stage infected cells expressing intermediate levels of CD..

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Grants

Awarded by CIHR foundation


Awarded by Canada Research Chair on Retroviral Entry


Funding Acknowledgements

This work was supported by a National Health and Medical Research Council Program Grant to S.J.K. This work was also supported by CIHR foundation grant 352417 to A.F. A.F. is the recipient of a Canada Research Chair on Retroviral Entry (grant RCHS0235). J.R. is the recipient of a Mathilde Krim Fellowship in Basic Biomedical Research from amfAR. J.P. is the recipient of a CIHR PhD fellowship award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.