Selective targeting of ITK blocks multiple steps of HIV replication

Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosi...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 105; no. 18; pp. 6684 - 6689
Main Authors Readinger, Julie A, Schiralli, Gillian M, Jiang, Jian-Kang, Thomas, Craig J, August, Avery, Henderson, Andrew J, Schwartzberg, Pamela L
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 06.05.2008
National Acad Sciences
Subjects
actin
Actins
Actins - metabolism
Antiretroviral agents
Biochemistry
Biological Sciences
calcium
Cell lines
CXCR4 receptor
DNA, Viral - metabolism
gene overexpression
HIV
HIV Envelope Protein gp120 - metabolism
HIV infections
HIV Infections - enzymology
HIV-1 - genetics
HIV-1 - physiology
Human immunodeficiency virus
Humans
Infections
Jurkat Cells
Kinases
mutants
Mutation
Protein-Tyrosine Kinases - antagonists & inhibitors
Proviruses - genetics
Reverse Transcription - genetics
Small interfering RNA
T cell receptors
T lymphocytes
Terminal Repeat Sequences - genetics
transcription factors
Transfection
tyrosine
Virion - enzymology
Virions
Virus Integration
Virus Internalization
Virus Replication
Viruses
Online AccessGet full text
ISSN0027-8424
1091-6490
1091-6490
DOI10.1073/pnas.0709659105

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Abstract Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCγ-1, Ca²⁺ mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
AbstractList Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLC ...-1, ... mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication. (ProQuest: ... denotes formulae/symbols omitted.)
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCγ-1, Ca²⁺ mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCgamma-1, Ca(2+) mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCgamma-1, Ca(2+) mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCgamma-1, Ca(2+) mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLC gamma -1, Ca super(2+) mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCγ-1, Ca 2+ mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCγ-1, Ca 2+ mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication. T cell signaling transcription tyrosine kinase viral entry kinase inhibitors
Author Henderson, Andrew J
Readinger, Julie A
Schwartzberg, Pamela L
August, Avery
Schiralli, Gillian M
Jiang, Jian-Kang
Thomas, Craig J
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Cites_doi 10.1021/jm00002a019
10.4049/jimmunol.174.3.1385
10.1128/AAC.38.4.668
10.1038/87979
10.1074/jbc.M312848200
10.1128/JVI.75.8.3779-3790.2001
10.1016/j.cub.2004.04.011
10.1038/ncb1610
10.1128/JVI.72.6.5251-5255.1998
10.1089/088922203769232610
10.1128/JVI.78.13.7138-7147.2004
10.1128/JVI.75.8.3626-3635.2001
10.1016/j.febslet.2006.04.023
10.1128/jvi.71.10.7253-7257.1997
10.1126/science.1061548
10.1128/JVI.01469-06
10.1006/meth.1997.0487
10.1016/0092-8674(89)90873-8
10.1016/S1074-7613(00)80115-6
10.1038/ni734
10.4049/jimmunol.174.8.4475
10.1038/nri1591
10.1128/JVI.77.22.12299-12309.2003
10.1128/jvi.70.9.6044-6053.1996
10.1038/sj.emboj.7601475
10.1016/0022-2836(67)90307-5
10.1111/j.1398-9219.2006.00428.x
10.1021/bi049428r
10.1016/S0092-8674(00)81823-1
10.1159/000078339
10.1128/AAC.44.6.1667-1673.2000
10.1073/pnas.0609771104
10.1073/pnas.042529199
10.1146/annurev.immunol.22.012703.104743
10.1126/science.8023143
10.1189/jlb.1105638
10.1023/B:VIRU.0000012260.32578.72
10.1126/science.1152725
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Author contributions: J.A.R. and G.M.S. contributed equally to this work; J.A.R., G.M.S., J.-K.J., C.J.T., A.A., A.J.H., and P.L.S. designed research; J.A.R. and G.M.S. performed research; J.-K.J. and C.J.T. contributed new reagents/analytic tools; J.A.R., G.M.S., A.J.H., and P.L.S. analyzed data; and J.A.R., G.M.S., A.J.H., and P.L.S. wrote the paper.
Edited by Stephen P. Goff, Columbia University College of Physicians and Surgeons, New York, NY, and approved March 19, 2008
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National Acad Sciences
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References e_1_3_3_17_2
e_1_3_3_16_2
e_1_3_3_19_2
e_1_3_3_38_2
e_1_3_3_18_2
e_1_3_3_13_2
e_1_3_3_36_2
e_1_3_3_12_2
e_1_3_3_37_2
e_1_3_3_15_2
e_1_3_3_34_2
e_1_3_3_14_2
e_1_3_3_35_2
e_1_3_3_32_2
e_1_3_3_33_2
e_1_3_3_11_2
e_1_3_3_30_2
e_1_3_3_10_2
e_1_3_3_31_2
e_1_3_3_6_2
e_1_3_3_5_2
e_1_3_3_8_2
e_1_3_3_7_2
e_1_3_3_28_2
e_1_3_3_9_2
e_1_3_3_27_2
e_1_3_3_29_2
e_1_3_3_24_2
e_1_3_3_23_2
e_1_3_3_26_2
e_1_3_3_25_2
e_1_3_3_2_2
e_1_3_3_20_2
e_1_3_3_1_2
e_1_3_3_4_2
e_1_3_3_22_2
e_1_3_3_3_2
e_1_3_3_21_2
15323564 - Biochemistry. 2004 Aug 31;43(34):11056-62
4291934 - J Mol Biol. 1967 Jun 14;26(2):365-9
8023143 - Science. 1994 Jul 8;265(5169):248-52
14585212 - AIDS Res Hum Retroviruses. 2003 Sep;19(9):817-23
9245614 - Methods. 1997 Aug;12(4):337-42
15123627 - J Biol Chem. 2004 Jul 9;279(28):29816-20
11329067 - Nat Med. 2001 May;7(5):631-4
16631752 - FEBS Lett. 2006 May 15;580(11):2691-7
16885500 - J Leukoc Biol. 2006 Oct;80(4):953-60
15803148 - Nat Rev Immunol. 2005 Apr;5(4):284-95
11830645 - Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1899-904
2676191 - Cell. 1989 Oct 6;59(1):103-12
16683918 - Traffic. 2006 Jun;7(6):731-45
14581566 - J Virol. 2003 Nov;77(22):12299-309
7913308 - Antimicrob Agents Chemother. 1994 Apr;38(4):668-74
10549622 - Immunity. 1999 Oct;11(4):399-409
11264367 - J Virol. 2001 Apr;75(8):3779-90
17170707 - EMBO J. 2007 Jan 10;26(1):41-52
18187620 - Science. 2008 Feb 15;319(5865):921-6
17420479 - Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6638-43
10817726 - Antimicrob Agents Chemother. 2000 Jun;44(6):1667-73
11520990 - Science. 2001 Aug 24;293(5534):1503-6
15661896 - J Immunol. 2005 Feb 1;174(3):1385-92
9311799 - J Virol. 1997 Oct;71(10):7253-7
15133303 - Int Arch Allergy Immunol. 2004 May;134(1):65-78
8709227 - J Virol. 1996 Sep;70(9):6044-53
17360745 - J Virol. 2007 Jun;81(11):5547-60
15186750 - Curr Biol. 2004 May 25;14(10):917-22
15194790 - J Virol. 2004 Jul;78(13):7138-47
14739648 - Virus Genes. 2004 Jan;28(1):5-18
11264352 - J Virol. 2001 Apr;75(8):3626-35
7830280 - J Med Chem. 1995 Jan 20;38(2):366-78
9573299 - J Virol. 1998 Jun;72(6):5251-5
15771581 - Annu Rev Immunol. 2005;23:549-600
17572668 - Nat Cell Biol. 2007 Jul;9(7):838-46
8980234 - Cell. 1996 Dec 27;87(7):1285-94
11702066 - Nat Immunol. 2001 Dec;2(12):1183-8
15814667 - J Immunol. 2005 Apr 15;174(8):4475-9
References_xml – ident: e_1_3_3_29_2
  doi: 10.1021/jm00002a019
– ident: e_1_3_3_9_2
  doi: 10.4049/jimmunol.174.3.1385
– ident: e_1_3_3_30_2
  doi: 10.1128/AAC.38.4.668
– ident: e_1_3_3_36_2
  doi: 10.1038/87979
– ident: e_1_3_3_7_2
  doi: 10.1074/jbc.M312848200
– ident: e_1_3_3_4_2
  doi: 10.1128/JVI.75.8.3779-3790.2001
– ident: e_1_3_3_8_2
  doi: 10.1016/j.cub.2004.04.011
– ident: e_1_3_3_2_2
  doi: 10.1038/ncb1610
– ident: e_1_3_3_12_2
  doi: 10.1128/JVI.72.6.5251-5255.1998
– ident: e_1_3_3_37_2
  doi: 10.1089/088922203769232610
– ident: e_1_3_3_3_2
  doi: 10.1128/JVI.78.13.7138-7147.2004
– ident: e_1_3_3_33_2
  doi: 10.1128/JVI.75.8.3626-3635.2001
– ident: e_1_3_3_16_2
  doi: 10.1016/j.febslet.2006.04.023
– ident: e_1_3_3_10_2
  doi: 10.1128/jvi.71.10.7253-7257.1997
– ident: e_1_3_3_1_2
  doi: 10.1126/science.1061548
– ident: e_1_3_3_5_2
  doi: 10.1128/JVI.01469-06
– ident: e_1_3_3_26_2
  doi: 10.1006/meth.1997.0487
– ident: e_1_3_3_17_2
  doi: 10.1016/0092-8674(89)90873-8
– ident: e_1_3_3_13_2
  doi: 10.1016/S1074-7613(00)80115-6
– ident: e_1_3_3_14_2
  doi: 10.1038/ni734
– ident: e_1_3_3_15_2
  doi: 10.4049/jimmunol.174.8.4475
– ident: e_1_3_3_22_2
  doi: 10.1038/nri1591
– ident: e_1_3_3_31_2
  doi: 10.1128/JVI.77.22.12299-12309.2003
– ident: e_1_3_3_27_2
  doi: 10.1128/jvi.70.9.6044-6053.1996
– ident: e_1_3_3_18_2
  doi: 10.1038/sj.emboj.7601475
– ident: e_1_3_3_35_2
  doi: 10.1016/0022-2836(67)90307-5
– ident: e_1_3_3_21_2
  doi: 10.1111/j.1398-9219.2006.00428.x
– ident: e_1_3_3_11_2
  doi: 10.1021/bi049428r
– ident: e_1_3_3_19_2
  doi: 10.1016/S0092-8674(00)81823-1
– ident: e_1_3_3_25_2
  doi: 10.1159/000078339
– ident: e_1_3_3_28_2
  doi: 10.1128/AAC.44.6.1667-1673.2000
– ident: e_1_3_3_32_2
  doi: 10.1073/pnas.0609771104
– ident: e_1_3_3_20_2
  doi: 10.1073/pnas.042529199
– ident: e_1_3_3_6_2
  doi: 10.1146/annurev.immunol.22.012703.104743
– ident: e_1_3_3_24_2
  doi: 10.1126/science.8023143
– ident: e_1_3_3_34_2
  doi: 10.1189/jlb.1105638
– ident: e_1_3_3_23_2
  doi: 10.1023/B:VIRU.0000012260.32578.72
– ident: e_1_3_3_38_2
  doi: 10.1126/science.1152725
– reference: 15194790 - J Virol. 2004 Jul;78(13):7138-47
– reference: 14739648 - Virus Genes. 2004 Jan;28(1):5-18
– reference: 11264367 - J Virol. 2001 Apr;75(8):3779-90
– reference: 7913308 - Antimicrob Agents Chemother. 1994 Apr;38(4):668-74
– reference: 17170707 - EMBO J. 2007 Jan 10;26(1):41-52
– reference: 11830645 - Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1899-904
– reference: 16683918 - Traffic. 2006 Jun;7(6):731-45
– reference: 11264352 - J Virol. 2001 Apr;75(8):3626-35
– reference: 16885500 - J Leukoc Biol. 2006 Oct;80(4):953-60
– reference: 11702066 - Nat Immunol. 2001 Dec;2(12):1183-8
– reference: 18187620 - Science. 2008 Feb 15;319(5865):921-6
– reference: 17360745 - J Virol. 2007 Jun;81(11):5547-60
– reference: 15814667 - J Immunol. 2005 Apr 15;174(8):4475-9
– reference: 2676191 - Cell. 1989 Oct 6;59(1):103-12
– reference: 15186750 - Curr Biol. 2004 May 25;14(10):917-22
– reference: 8023143 - Science. 1994 Jul 8;265(5169):248-52
– reference: 9311799 - J Virol. 1997 Oct;71(10):7253-7
– reference: 15803148 - Nat Rev Immunol. 2005 Apr;5(4):284-95
– reference: 15133303 - Int Arch Allergy Immunol. 2004 May;134(1):65-78
– reference: 15123627 - J Biol Chem. 2004 Jul 9;279(28):29816-20
– reference: 16631752 - FEBS Lett. 2006 May 15;580(11):2691-7
– reference: 14585212 - AIDS Res Hum Retroviruses. 2003 Sep;19(9):817-23
– reference: 9245614 - Methods. 1997 Aug;12(4):337-42
– reference: 8980234 - Cell. 1996 Dec 27;87(7):1285-94
– reference: 8709227 - J Virol. 1996 Sep;70(9):6044-53
– reference: 11329067 - Nat Med. 2001 May;7(5):631-4
– reference: 14581566 - J Virol. 2003 Nov;77(22):12299-309
– reference: 7830280 - J Med Chem. 1995 Jan 20;38(2):366-78
– reference: 15661896 - J Immunol. 2005 Feb 1;174(3):1385-92
– reference: 10817726 - Antimicrob Agents Chemother. 2000 Jun;44(6):1667-73
– reference: 17420479 - Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6638-43
– reference: 9573299 - J Virol. 1998 Jun;72(6):5251-5
– reference: 15771581 - Annu Rev Immunol. 2005;23:549-600
– reference: 4291934 - J Mol Biol. 1967 Jun 14;26(2):365-9
– reference: 15323564 - Biochemistry. 2004 Aug 31;43(34):11056-62
– reference: 10549622 - Immunity. 1999 Oct;11(4):399-409
– reference: 17572668 - Nat Cell Biol. 2007 Jul;9(7):838-46
– reference: 11520990 - Science. 2001 Aug 24;293(5534):1503-6
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Snippet Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed...
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StartPage 6684
SubjectTerms actin
Actins
Actins - metabolism
Antiretroviral agents
Biochemistry
Biological Sciences
calcium
Cell lines
CXCR4 receptor
DNA, Viral - metabolism
gene overexpression
HIV
HIV Envelope Protein gp120 - metabolism
HIV infections
HIV Infections - enzymology
HIV-1 - genetics
HIV-1 - physiology
Human immunodeficiency virus
Humans
Infections
Jurkat Cells
Kinases
mutants
Mutation
Protein-Tyrosine Kinases - antagonists & inhibitors
Proviruses - genetics
Reverse Transcription - genetics
Small interfering RNA
T cell receptors
T lymphocytes
Terminal Repeat Sequences - genetics
transcription factors
Transfection
tyrosine
Virion - enzymology
Virions
Virus Integration
Virus Internalization
Virus Replication
Viruses
Title Selective targeting of ITK blocks multiple steps of HIV replication
URI https://www.jstor.org/stable/25461854
http://www.pnas.org/content/105/18/6684.abstract
https://www.ncbi.nlm.nih.gov/pubmed/18443296
https://www.proquest.com/docview/201410386
https://www.proquest.com/docview/20847671
https://www.proquest.com/docview/47651547
https://www.proquest.com/docview/69195855
https://pubmed.ncbi.nlm.nih.gov/PMC2365562
Volume 105
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