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PMID: 20231400 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Persistent interactions between biguanide-based compound NB325 and CXCR4 result in prolonged inhibition of human immunodeficiency virus type 1 infection.

Antimicrobial agents and chemotherapy ·Vol. 54 ·No. 5 ·2010-05-00 ·Pages 1965-72

Thakkar N, Pirrone V, Passic S, Keogan S, Zhu W, Kholodovych V, Welsh W, Rando R, Labib M, Wigdahl B, Krebs FC

Abstract

We previously demonstrated that the biguanide-based compound NB325 inhibits human immunodeficiency virus type 1 (HIV-1) infection by interacting with the CXCR4 viral coreceptor. This interaction also appeared to be persistent, since HIV-1 infection was inhibited even when the virus was introduced subsequent to the removal of NB325 from the cell culture medium. The present studies were conducted to determine the extent and mechanism of this prolonged antiviral activity. Persistent inhibition of HIV-1 infection by NB325 was concentration dependent and was apparent up to 8 h after removal of the compound. Flow cytometric analyses of stimulated CD4(+) T lymphocytes exposed to NB325 demonstrated concentration-dependent reductions in CXCR4 extracellular loop 2 epitope recognition that were maintained up to 24 h after removal of the compound. CXCL12-induced chemotaxis was also persistently inhibited following pre-exposure to NB325. These results demonstrate that persistent inhibition of X4 HIV-1 infection by NB325 involves extended perturbation of the viral coreceptor CXCR4.

MeSH Terms
Antiviral Agents/metabolism,pharmacology,toxicity Biguanides/metabolism,pharmacology,toxicity CD4-Positive T-Lymphocytes/cytology,metabolism,virology Cells, Cultured Chemotaxis, Leukocyte/drug effects,physiology Epitopes/drug effects Flow Cytometry HIV Infections/drug therapy,metabolism HIV-1/drug effects Humans Inhibitory Concentration 50 Receptors, CXCR4/metabolism
Chemicals
Antiviral Agents Biguanides CXCR4 protein, human Epitopes NB325 Receptors, CXCR4
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Thakkar Nina
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Pirrone Vanessa
Passic Shendra
Keogan Shawn
Zhu Wei
Kholodovych Vladyslav
Welsh William
Rando Robert
Labib Mohamed
Wigdahl Brian
Krebs Fred C
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
1098-6596
DOI
10.1128/AAC.00934-09
Published
2010-05-00
Epub
2010-00-15
Pages
1965-72
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC2863618
Subset
IM
Grants
NIAID NIH HHS · U19 AI076965 · United States
NIAID NIH HHS · 1 U19 AI076965 · United States
External Links
PubMed source DOI: 10.1128/AAC.00934-09 PMC Full Text View journal details
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