Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Keggin Polyoxometalate

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Abstract

Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K ₆HPTi ₂W ₁₀O ₄₀). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus. Surface plasmon resonance binding assays and flow cytometry analysis showed that PT-1 blocked the gp120 binding site in the CD4 receptor. Moreover, PT-1 bound directly to gp41 NHR (N36 peptide), thereby interrupting the core bundle formation of gp41. In conclusion, our data suggested that PT-1 may be developed as a new anti-HIV-1 agent through its effects on entry inhibition.

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Most cited references 44

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Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene.

M Emerman, Amanda Kimpton (1992)

We have constructed a HeLa cell line that both expresses high levels of CD4 and contains a single integrated copy of a beta-galactosidase gene that is under the control of a truncated human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). This cell line, called CD4-LTR/beta-gal, can be used to determine quantitatively the titer of laboratory-adapted HIV strains, and the method used to do so is as sensitive as the determination of viral titers in a T-cell line by end point dilution. Using this cell line as a titer system, we calculated that HIV-1 stocks contain only one infectious particle per 3,500 to 12,000 virions. Virus derived from a molecular clone of a macrophagetropic provirus will not infect this cell line. We have also cocultivated peripheral blood lymphocyte cultures from HIV-infected individuals with the CD4-LTR/beta-gal indicator cells. In a majority of primary isolates (five of eight), including isolates from asymptomatic patients, rare virus-infected cells that can activate the beta-galactosidase gene are present.

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A time-of–drug addition approach to target identification of antiviral compounds

Dirk Daelemans, Rudi Pauwels, Erik De Clercq … (2011)

Insight into the mode of action of newly discovered antiviral agents is now almost a prerequisite for clinical development. This protocol describes a method that provides information on the target of inhibitors of the human immunodeficiency virus (HIV); it can also be adapted to other viruses. The results from this experiment are available within 2 d. This time-based approach determines how long the addition of a compound can be postponed before losing its antiviral activity in cell culture. The target of an antiviral compound can be identified by comparing its relative position in the time scale to that of reference drugs. Therefore, it is more precise than, for example, in the case of HIV, a determination of pre- or postintegrational mode of action, and combines in one routine different assays for studying mechanisms of action.

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HIV entry: a game of hide-and-fuse?

Gregory Melikyan (2014)

Human Immunodeficiency Virus (HIV) initiates infection by fusing its envelope membrane with the cell membrane through a process which is triggered through interactions with the cellular receptor and coreceptor. Although the mechanism of HIV fusion has been extensively studied, the point of its entry into cells remains controversial. HIV has long been thought to fuse directly with the cell plasma membrane. However, several lines of evidence suggest that endocytic entry of HIV can lead to infection and, moreover, that endocytosis could be the predominant HIV entry pathway into different cell types. This review discusses recent findings pertinent to HIV entry routes and novel approaches to pinpoint the sites of virus entry. Copyright © 2013 Elsevier B.V. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 16 May 2018

Publication date Collection: May 2018

Volume: 10

Issue: 5

Electronic Location Identifier: 265

Affiliations

[1 ]College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; wangxiaoli@ 123456bjut.edu.cn (X.W.); zwm1436271046@ 123456sina.com (W.Z.); liboye1994@ 123456sina.com (B.L.); zhuying19901101@ 123456163.com (Y.Z.); yishu-y@ 123456bjut.edu.cn (Y.Y.); hongyan@ 123456bjut.edu.cn (H.Y.)

[2 ]National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; wangjiao1018@ 123456hotmail.com

Author notes

[* ]Correspondence: hq07616@ 123456bjut.edu.cn (Q.H.); xgzhang01@ 123456163.com (X.Z.); zengyicdc@ 123456sina.com (Y.Z.)

[†]

These authors contributed equally to this work.

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Boye Li https://orcid.org/0000-0002-1923-4013

Qin Hu https://orcid.org/0000-0003-1196-879X

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Publisher ID: viruses-10-00265

DOI: 10.3390/v10050265

PMC ID: 5977258

PubMed ID: 29772712

SO-VID: 47f8f755-4019-450a-9961-965a154b9704

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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 ( http://creativecommons.org/licenses/by/4.0/).

Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Keggin Polyoxometalate

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MDPI: Coronavirus

Most cited references 44

Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene.

A time-of–drug addition approach to target identification of antiviral compounds

HIV entry: a game of hide-and-fuse?

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