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HIV‐1 Replication Is Stimulated by Sodium Stibogluconate, the Therapeutic Mainstay in the Treatment of Leishmaniasis

HIV‐1 Replication Is Stimulated by Sodium Stibogluconate, the Therapeutic Mainstay in the... Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound sodium stibogluconate is a drug of choice for the treatment of leishmaniasis. Because sodium stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV‐1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory‐adapted and clinical strains of HIV‐1, we report that sodium stibogluconate induces an increase in HIV‐1 transcription and virus replication in primary CD4+ T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor-κB and activator protein 1, as well as the Syk, Jun, and mitogen‐activated protein kinase/extracellular signal‐related kinase signal‐transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV‐1-infected patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Infectious Diseases Oxford University Press

HIV‐1 Replication Is Stimulated by Sodium Stibogluconate, the Therapeutic Mainstay in the Treatment of Leishmaniasis

Journal of Infectious Diseases , Volume 195 (2) – Jan 15, 2007
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References (40)

Publisher
Oxford University Press
Copyright
© Published by Oxford University Press.
Subject
Major articles
ISSN
0022-1899
eISSN
1537-6613
DOI
10.1086/510398
pmid
17191169
Publisher site
See Article on Publisher Site

Abstract

Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound sodium stibogluconate is a drug of choice for the treatment of leishmaniasis. Because sodium stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV‐1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory‐adapted and clinical strains of HIV‐1, we report that sodium stibogluconate induces an increase in HIV‐1 transcription and virus replication in primary CD4+ T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor-κB and activator protein 1, as well as the Syk, Jun, and mitogen‐activated protein kinase/extracellular signal‐related kinase signal‐transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV‐1-infected patients.

Journal

Journal of Infectious Diseases – Oxford University Press

Published: Jan 15, 2007

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