In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection

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In efforts to define the potential role of innate immune effector mechanisms in influencing the course of SIV infection during the acute infection period, our lab utilized the in vivo daily administration of 20 mg/kg orally of a compound called Tofacitinib (a Janus kinase 3 inhibitor) to a group of 15 rhesus macaques starting at day −6 and until day 28 post intravenous SIVmac239 infection. An additional group of 16 similarly SIV infected rhesus macaques served as a placebo control. This drug targets the JAK/STAT pathway that is utilized by cells including the NK cell lineage, a major cell of the innate immune system. The dosage utilized was based on extensive previous PK studies that resulted in a marked depletion of the NK cells. Of interest while such drug administration had no effect on plasma viral loads during acute infection, such drug administration led to significant increases in plasma and gastro-intestinal tissues (GIT) viral loads during chronic infection. A series of phenotypic/functional studies were performed to determine the mechanisms for this delayed effect and the correlates identified. These data are the first to document the effect of JAK-3 inhibitor during acute SIV infection with implications for HIV vaccine design.

Vyšlo v časopise: In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003929
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003929

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