c-SRC protein tyrosine kinase regulates early HIV-1 infection post-entry

AIDS
Stephen D S McCarthyD R Branch

Abstract

We investigated whether HIV-1 inhibition by SRC-family kinase inhibitors is through the non-receptor tyrosine kinase pp60 (c-SRC) and its binding partner, protein tyrosine kinase 2 beta (PTK2B). CD4 T-lymphocytes were infected with R5 (JR-FL) or X4 (HXB2) HIV-1. We used SRC-family kinase inhibitors or targeted siRNA knockdown of c-SRC and PTK2B, then monitored effects on the early HIV-1 lifecycle. Four SRC-family kinase inhibitors or targeted siRNA knockdown were used to reduce c-SRC or PTK2B protein expression. Activated CD4 T-lymphocytes were infected with recombinant, nef-deficient, or replication-competent infectious viruses. Knockdown experiments examined early infection by monitoring: luciferase activity, expression of host surface receptors, reverse transcriptase activity, p24 levels and qPCR of reverse transcripts, integrated HIV-1, and two-long terminal repeat (2-LTR) circles. All SRC-family kinase inhibitors inhibited R5 and X4 HIV-1 infection. Neither c-SRC nor PTK2B siRNA knockdown had an effect on cell surface receptors (CD4, CXCR4, and CCR5) nor on reverse transcriptase activity. However, using JR-FL both decreased luciferase activity while increasing late reverse transcripts (16-fold) and 2-LTR circles (eight-fol...Continue Reading

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Citations

Oct 29, 2019·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Stephen D S McCarthyRaymond W Wong
May 12, 2017·Frontiers in Neuroscience·Monique E MaubertMichael R Nonnemacher
Oct 18, 2019·Frontiers in Pharmacology·José Rivera-Torres, Esther San José
Jun 16, 2017·American Journal of Physiology. Renal Physiology·Jun Wang, Shougang Zhuang

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Methods Mentioned

BETA
FACS
pull-down
Immunoprecipitation

Clinical Trials Mentioned

NCT00610714
NCT01764087

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