SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Fusion Proteins CLD and CLDmut Demonstrate Potent and Broad Neutralizing Activity against HIV-1.

Fu, M; Xiao, Y; Du, T; Hu, H; Ni, F; Hu, K; Hu, Q (2022) Fusion Proteins CLD and CLDmut Demonstrate Potent and Broad Neutralizing Activity against HIV-1. Viruses, 14 (7). p. 1365. ISSN 1999-4915 https://doi.org/10.3390/v14071365
SGUL Authors: Hu, Qinxue

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
[img] Archive (ZIP) (Supplementary Material) Published Version
Available under License Creative Commons Attribution.

Download (902kB)

Abstract

HIV-1 envelope glycoprotein (Env) interacts with cellular receptors and mediates virus entry into target cells. Blocking Env-receptor interactions represents an effective interventional strategy for developing HIV-1 entry inhibitors. We previously designed a panel of CD4-linker-DC-SIGN (CLD) constructs by fusing the extracellular CD4 and DC-SIGN domains with various linkers. Such CLDs produced by the prokaryotic system efficiently inhibited HIV-1 infection and dissemination in vitro and ex vivo. In this study, following the construction and identification of the most promising candidate with a linker of 8 Gly4Ser repeats (named CLD), we further designed an improved form (named CLDmut) by back mutating Cys to Ser at amino acid 60 of CD4. Both CLD and CLDmut were produced in mammalian (293F) cells for better protein translation and modification. The anti-HIV-1 activity of CLD and CLDmut was assessed against the infection of a range of HIV-1 isolates, including transmitted and founder (T/F) viruses. While both CLD and CLDmut efficiently neutralized the tested HIV-1 isolates, CLDmut demonstrated much higher neutralizing activity than CLD, with an IC50 up to one log lower. The neutralizing activity of CLDmut was close to or more potent than those of the highly effective HIV-1 broadly neutralizing antibodies (bNAbs) reported to date. Findings in this study indicate that mammalian cell-expressed CLDmut may have the potential to be used as prophylaxis or/and therapeutics against HIV-1 infection.

Item Type: Article
Additional Information: Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: CD4, CLD, CLDmut, DC-SIGN, HIV-1, bNAbs, Animals, Antibodies, Neutralizing, CD4 Antigens, Cell Adhesion Molecules, HIV Antibodies, HIV Envelope Protein gp120, HIV Infections, HIV Seropositivity, HIV-1, Humans, Lectins, C-Type, Mammals, Receptors, Cell Surface, env Gene Products, Human Immunodeficiency Virus, Animals, Mammals, Humans, HIV-1, HIV Infections, HIV Seropositivity, Cell Adhesion Molecules, Lectins, C-Type, Receptors, Cell Surface, HIV Envelope Protein gp120, HIV Antibodies, env Gene Products, Human Immunodeficiency Virus, Antibodies, Neutralizing, CD4 Antigens, HIV-1, CD4, DC-SIGN, CLD, CLDmut, bNAbs, 0605 Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Viruses
ISSN: 1999-4915
Language: eng
Dates:
DateEvent
23 June 2022Published
20 June 2022Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
81772192National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
82171736National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
2018ZX10301406-002National Mega-Projects against Infectious DiseasesUNSPECIFIED
PubMed ID: 35891347
Web of Science ID: WOS:000831864600001
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/114644
Publisher's version: https://doi.org/10.3390/v14071365

Actions (login required)

Edit Item Edit Item