HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic mainstay in the treatment of leishmaniasis.
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- kappa B 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.
Barat
Corinne
C
Research Center in Infectious Diseases, Centre Hospitalier de l'Universite Laval Research Center, and Faculty of Medicine, Universite Laval, Quebec, Canada.
Zhao
Chenqi
C
Ouellette
Marc
M
Tremblay
Michel J
MJ
D000967:Antimony Sodium Gluconate / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000821:virology; D009924:Organ Culture Techniques / Q000379:methods; D013950:Thymus Gland / Q000166:cytology / Q000821:virology; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000981:Antiprotozoal Agents; D014764:Viral Proteins; D000967:Antimony Sodium Gluconate