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Sci Rep. 2018 Feb 16;8(1):3217. doi: 10.1038/s41598-018-21344-7.

IL-2 Inducible Kinase ITK is Critical for HIV-1 Infection of Jurkat T-cells.

Author information

1
Clinic for Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, 40225, Germany.
2
Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, 40225, Germany.
3
Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, 40223, Germany.
4
Clinic for Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, 40225, Germany. carsten.muenk@med.uni-duesseldorf.de.

Abstract

Successful replication of Human immunodeficiency virus (HIV)-1 depends on the expression of various cellular host factors, such as the interleukin-2 inducible T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK is selectively expressed in T-cells and coordinates signaling pathways downstream of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca2+-release, transcription factor mobilization, and actin rearrangements. The exact role of ITK during HIV-1 infection is still unknown. We analyzed the function of ITK during HIV-1 replication and showed that attachment, fusion of virions with the cell membrane and entry into Jurkat T-cells was inhibited when ITK was knocked down. In contrast, reverse transcription and provirus expression were not affected by ITK deficiency. Inhibited ITK expression did not affect the CXCR4 receptor on the cell surface, whereas CD4 and LFA-1 integrin levels were slightly enhanced in ITK knockdown cells and heparan sulfate (HS) expression was completely abolished in ITK depleted T-cells. However, neither HS expression nor other attachment factors could explain the impaired HIV-1 binding to ITK-deficient cells, which suggests that a more complex cellular process is influenced by ITK or that not yet discovered molecules contribute to restriction of HIV-1 binding and entry.

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