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13 results on '"Kozlowski, Hannah N."'

3. Genotyping SARS-CoV-2 Variants Using Ratiometric Nucleic Acid Barcode Panels

Author

Kozlowski, Hannah N., primary, Malekjahani, Ayden, additional, Li, Vanessa Y. C., additional, Lekuti, Ayokunle A., additional, Perusini, Stephen, additional, Bell, Natalie G., additional, Voisin, Veronique, additional, Pouyabahar, Delaram, additional, Pai, Shraddha, additional, Bader, Gary D., additional, Mubareka, Samira, additional, Gubbay, Jonathan B., additional, and Chan, Warren C. W., additional

Published
2023
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9. Diagnosing COVID-19: The Disease and Tools for Detection

Author

Udugama, Buddhisha, primary, Kadhiresan, Pranav, additional, Kozlowski, Hannah N., additional, Malekjahani, Ayden, additional, Osborne, Matthew, additional, Li, Vanessa Y. C., additional, Chen, Hongmin, additional, Mubareka, Samira, additional, Gubbay, Jonathan B., additional, and Chan, Warren C. W., additional

Published
2020
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13. Targeting ABL1 or ARG Tyrosine Kinases to Restrict HIV-1 Infection in Primary CD4+ T-Cells or in Humanized NSG Mice.

Author

McCarthy SDS, Leontyev D, Nicoletti P, Binnington B, Kozlowski HN, Ostrowski M, Cochrane A, Branch DR, and Wong RW

Subjects
Animals, CD4-Positive T-Lymphocytes immunology, Dasatinib therapeutic use, Female, HIV Infections immunology, Humans, Male, Mice, Mice, Inbred NOD, Protein-Tyrosine Kinases physiology, Proto-Oncogene Proteins c-abl physiology, RNA, Small Interfering genetics, HIV Infections drug therapy, HIV-1 drug effects, Protein Kinase Inhibitors therapeutic use, Protein-Tyrosine Kinases antagonists & inhibitors, Proto-Oncogene Proteins c-abl antagonists & inhibitors
Abstract

Background: Previous studies support dasatinib as a potent inhibitor of HIV-1 replication. However, a functional distinction between 2 kinase targets of the drug, ABL1 and ARG, has not been assessed., Setting: We used primary CD4 T-cells, CD8-depleted peripheral blood mononuclear cells (PBMCs) from a treatment naïve HIV-1 patient, and a humanized mouse model of HIV-1 infection. We assessed the roles of ABL1 and ARG during HIV-1 infection and use of dasatinib as a potential antiviral against HIV-1 in humanized mice., Methods: Primary CD4 T-cells were administered siRNA targeting ABL1 or ARG, then infected with HIV-1 containing luciferase reporter viruses. Quantitative polymerase chain reaction of viral integration of 4 HIV-1 strains was also assessed. CD8-depleted PBMCs were treated for 3 weeks with dasatinib. NSG mice were engrafted with CD34 pluripotent stem cells from human fetal cord blood, and infected with Ba-L virus after 19 weeks. Mice were treated daily with dasatinib starting 5 weeks after infection., Results: siRNA knockdown of ABL1 or ARG had no effect on viral reverse transcripts, but increased 2-LTR circles 2- to 4-fold and reduced viral integration 2- to 12-fold. siRNA knockdown of ARG increased SAMHD1 activation, whereas knockdown of either kinase reduced RNA polymerase II activation. Treating CD8-depleted PBMCs from a treatment-naïve patient with 50 nM of dasatinib for 3 weeks reduced p24 levels by 99.8%. Ba-L (R5)-infected mice injected daily with dasatinib showed a 95.1% reduction in plasma viral load after 2 weeks of treatment., Conclusions: We demonstrate a novel nuclear role for ABL1 and ARG in ex vivo infection experiments, and proof-of-principle use of dasatinib in a humanized mouse model of HIV-1 infection.

Published
2019
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