ArticlePLoS pathogens2014
In vivo administration of a JAK3 inhibitor during acute SIV infection leads to significant increases in viral load during chronic infection.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Post-translational modification of NK cell receptors offers clues to antigenic specificity riddle.Frontiers in immunology · 2025Review
- NK cells modulate in vivo control of SARS-CoV-2 replication and suppression of lung damage.PLoS pathogens · 2024Article
- Review
- Non-human Primate Determinants of Natural Killer Cells in Tissues at Steady-State and During Simian Immunodeficiency Virus Infection.Frontiers in immunology · 2020Article
- Adaptive features of innate immune cells and their relevance to graft rejection.Current opinion in organ transplantation · 2019Review
- Type I interferon signaling, regulation and gene stimulation in chronic virus infection.Seminars in immunology · 2019Review
- Optimizing intracellular signaling domains for CAR NK cells in HIV immunotherapy: a comprehensive review.Drug discovery today · 2019Review
- Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections.Frontiers in immunology · 2019Review
- JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation.Frontiers in immunology · 2019Review
- CMV Primes Functional Alternative Signaling in Adaptive Δg NK Cells but Is Subverted by Lentivirus Infection in Rhesus Macaques.Cell reports · 2018Article
- JAK/STAT signaling in regulation of innate lymphoid cells: The gods before the guardians.Immunological reviews · 2018Review
- SIV/SHIV-Zika co-infection does not alter disease pathogenesis in adult non-pregnant rhesus macaque model.PLoS neglected tropical diseases · 2018Article
- In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques.Journal of neurovirology · 2018Article
- Tracking KLRC2 (NKG2C)+ memory-like NK cells in SIV+ and rhCMV+ rhesus macaques.PLoS pathogens · 2018Article
- Redefining Memory: Building the Case for Adaptive NK Cells.Journal of virology · 2017Review
- Memory responses of natural killer cells.Seminars in immunology · 2017Review
- Effect of Anti-IL-15 Administration on T Cell and NK Cell Homeostasis in Rhesus Macaques.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- HMGB1 Is Involved in IFN-α Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells.PLoS pathogens · 2016Article
- Natural Killer Cell Memory.Immunity · 2015Review
- Antigen-specific NK cell memory in rhesus macaques.Nature immunology · 2015Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8⁺ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4⁺ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a⁺ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses.
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