Engineered CD4 T Cells Expressing a Membrane Anchored Viral Inhibitor Restrict HIV-1 Through Cis and Trans Mechanisms

Authors

Weiming Wang
Khanghy Truong
Chaobaihui Ye
Suman Sharma
Huan He
Lihong Liu
Michael Wen
Anisha Misra
Paul Zhou
Jason T Kimata

Publication Date

1-1-2023

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2023.1167965

PMID

37781368

PMCID

PMC10538569

PubMedCentral® Posted Date

9-14-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, HIV-1, CD4-Positive T-Lymphocytes, HIV Infections, HIV Antibodies, Cell Line, HIV Seropositivity, Single-Chain Antibodies, HIV, CD4 + T cells, dendritic cells, neutralization, single chain variable fragments, glycosyl phosphatidylinositol, immunotherapy

Abstract

HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4

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