Potent inhibition of HIV-1 entry by (s4dU)35

András Horváth, Szilvia Tokés, Tracy Hartman, Karen Watson, Jim A. Turpin, Robert W. Buckheit, Zsolt Sebestyén, J. Szöllősi, Ilona Benko, Thomas J. Bardos, Joseph A. Dunn, L. Fésüs, F. Tóth, J. Aradi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We have previously reported the potent in vitro HIV-1 anti-reverse transcriptase activity of a 35-mer of 4-thio-deoxyuridylate [(s 4dU)35]. In efforts to define its activity in a more physiological system, studies were carried out to determine the stage of viral infection that this compound mediates its anti-viral effect. Results of the studies reported herein show that (s4dU)35 is nontoxic and is capable of inhibiting both single and multi-drug resistant HIV strains (IC50: 0.8-25.4 μg/ml) in vitro. Besides its previously reported anti-RT activity, (s4dU)35 mediated its antiviral action by preventing virus attachment (IC50: 0.002-0.003 μg/ml), and was stable in vitro and slowly degraded by DNAses. Competition studies and fluorescence resonance energy transfer (FRET) experiments indicated that (s 4dU)35 preferentially binds to CD4 receptors, but not to CD48. Confocal laser scanning microscopy (CLSM) studies showed that (s 4dU)35 did not penetrate into the cells and colocalized with cell surface thioredoxin. Our studies identify (s4dU) 35 as a potential novel HIV entry inhibitor that may have utility as either a systemic antiretroviral or as a preventing agent for HIV transmission.

Original languageEnglish
Pages (from-to)214-223
Number of pages10
JournalVirology
Volume334
Issue number2
DOIs
Publication statusPublished - Apr 10 2005

Fingerprint

HIV-1
Inhibitory Concentration 50
HIV Fusion Inhibitors
HIV
Virus Attachment
CD4 Antigens
Fluorescence Resonance Energy Transfer
Thioredoxins
Deoxyribonucleases
Virus Diseases
Confocal Microscopy
Antiviral Agents
Pharmaceutical Preparations
(s4dU)35
In Vitro Techniques
Human immunodeficiency virus 1 reverse transcriptase

Keywords

  • CD4
  • HIV-entry
  • Inhibition
  • Oligonucleotide
  • Redox process

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Horváth, A., Tokés, S., Hartman, T., Watson, K., Turpin, J. A., Buckheit, R. W., ... Aradi, J. (2005). Potent inhibition of HIV-1 entry by (s4dU)35. Virology, 334(2), 214-223. https://doi.org/10.1016/j.virol.2005.01.033

Potent inhibition of HIV-1 entry by (s4dU)35. / Horváth, András; Tokés, Szilvia; Hartman, Tracy; Watson, Karen; Turpin, Jim A.; Buckheit, Robert W.; Sebestyén, Zsolt; Szöllősi, J.; Benko, Ilona; Bardos, Thomas J.; Dunn, Joseph A.; Fésüs, L.; Tóth, F.; Aradi, J.

In: Virology, Vol. 334, No. 2, 10.04.2005, p. 214-223.

Research output: Contribution to journalArticle

Horváth, A, Tokés, S, Hartman, T, Watson, K, Turpin, JA, Buckheit, RW, Sebestyén, Z, Szöllősi, J, Benko, I, Bardos, TJ, Dunn, JA, Fésüs, L, Tóth, F & Aradi, J 2005, 'Potent inhibition of HIV-1 entry by (s4dU)35', Virology, vol. 334, no. 2, pp. 214-223. https://doi.org/10.1016/j.virol.2005.01.033
Horváth A, Tokés S, Hartman T, Watson K, Turpin JA, Buckheit RW et al. Potent inhibition of HIV-1 entry by (s4dU)35. Virology. 2005 Apr 10;334(2):214-223. https://doi.org/10.1016/j.virol.2005.01.033
Horváth, András ; Tokés, Szilvia ; Hartman, Tracy ; Watson, Karen ; Turpin, Jim A. ; Buckheit, Robert W. ; Sebestyén, Zsolt ; Szöllősi, J. ; Benko, Ilona ; Bardos, Thomas J. ; Dunn, Joseph A. ; Fésüs, L. ; Tóth, F. ; Aradi, J. / Potent inhibition of HIV-1 entry by (s4dU)35. In: Virology. 2005 ; Vol. 334, No. 2. pp. 214-223.
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