Back to Search
Start Over
Inhibition of the thioredoxin system by PX-12 (1-methylpropyl 2-imidazolyl disulfide) impedes HIV-1 infection in TZM-bl cells
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Human immunodeficiency virus (HIV-1) entry is initiated by the binding between the viral envelope glycoprotein gp120 and the host receptor CD4, and followed by reduction of structural disulfides of gp120 and CD4. The host thioredoxin-1 (Trx1) efficiently reduces disulfides of gp120 and CD4 in vitro, and recently CD4-dependent HIV-1 entry was shown to be inhibited by anti-Trx1-antibodies, indicating a central role for Trx1. 1-methylpropyl-2-imidazolyl disulfide (PX-12) is a reversible inhibitor of the Trx1 system that may also cause a slow irreversible thioalkylation of Trx1. It was developed as an antitumor agent, however, the current study aimed to determine if it also has an anti-HIV-1 effect. We show that PX-12 has anti-HIV-1(IIIB) activity in TZM-bl cells, in fact, no virus was detected inside the cells in the presence of 10 µM PX-12. Moreover, PX-12 inhibited the enzymatic activity of Trx1 and the Trx1-dependent disulfide reduction of gp120. Microtubule polymerization and formation of acetylated microtubules were also inhibited, activities shown to be required for HIV-1 life cycle propagation. In conclusion, our data strengthens the notion that the early steps of the HIV-1 life cycle depends on the Trx1 system and indicate that the Trx1 system may be a rational drug target for HIV-1 treatment.
- Subjects :
- 0301 basic medicine
lcsh:Medicine
HIV Infections
Plasma protein binding
HIV Envelope Protein gp120
Article
Virus
Cell Line
Microtubule polymerization
03 medical and health sciences
Thioredoxins
0302 clinical medicine
Viral envelope
Humans
Disulfides
Receptor
lcsh:Science
Multidisciplinary
Chemistry
lcsh:R
Imidazoles
virus diseases
Virus Internalization
In vitro
Cell biology
030104 developmental biology
Cell culture
CD4 Antigens
HIV-1
lcsh:Q
Thioredoxin
Oxidation-Reduction
030217 neurology & neurosurgery
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....9c93e8019bca071c4940a406912da544