Skip to main content
Top
Published in: Virology Journal 1/2012

Open Access 01-12-2012 | Research

Human immunodeficiency virus type 1 Vpu and cellular TASK proteins suppress transcription of unintegrated HIV-1 DNA

Authors: Nkiruka Emeagwali, James EK Hildreth

Published in: Virology Journal | Issue 1/2012

Login to get access

Abstract

Background

Unintegrated HIV-1 DNA serves as transcriptionally active templates in HIV-infected cells. Several host factors including NF-κβ enhance HIV-1 transcription. HIV-1 induced NF-κβ activation can be suppressed by viral protein U (Vpu). Interestingly HIV-1 Vpu shares amino acid homology with cellular Twik-related Acid Sensitive K+ (TASK) channel 1 and the proteins physically interact in cultured cells and AIDS lymphoid tissue. Furthermore, the first transmembrane domain of TASK-1 is functionally interchangeable with Vpu and like Vpu enhances HIV-1 release.

Results

Here we further characterize the role of TASK channels and Vpu in HIV-1 replication. We demonstrate that both TASK channels and Vpu can preferentially inhibit transcription of unintegrated HIV-1 DNA. Interestingly, TASK-1 ion channel function is not required and suppression of HIV-1 transcription by TASK-1 and Vpu was reversed by overexpression of RelA (NF-κβ p65).

Conclusion

TASK proteins and Vpu suppress transcription of unintegrated HIV-1 DNA through an NF-κβ-dependent mechanism. Taken together these findings support a possible physiological role for HIV-1 Vpu and TASK proteins as modulators of transcription of unintegrated HIV-1 DNA genomes.
Appendix
Available only for authorised users
Literature
1.
go back to reference Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, et al.: Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 1997, 387: 183-188.PubMedCrossRef Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, et al.: Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 1997, 387: 183-188.PubMedCrossRef
2.
go back to reference Sawyer SL, Malik HS: Positive selection of yeast nonhomologous end-joining genes and a retrotransposon conflict hypothesis. Proc Natl Acad Sci U S A 2006, 103: 17614-17619.PubMedPubMedCentralCrossRef Sawyer SL, Malik HS: Positive selection of yeast nonhomologous end-joining genes and a retrotransposon conflict hypothesis. Proc Natl Acad Sci U S A 2006, 103: 17614-17619.PubMedPubMedCentralCrossRef
3.
go back to reference Demogines A, East AM, Lee JH, Grossman SR, Sabeti PC, Paull TT, Sawyer SL: Ancient and recent adaptive evolution of primate non-homologous end joining genes. PLoS Genet 2010, 6: e1001169.PubMedPubMedCentralCrossRef Demogines A, East AM, Lee JH, Grossman SR, Sabeti PC, Paull TT, Sawyer SL: Ancient and recent adaptive evolution of primate non-homologous end joining genes. PLoS Genet 2010, 6: e1001169.PubMedPubMedCentralCrossRef
4.
go back to reference Farnet CM, Haseltine WA: Circularization of human immunodeficiency virus type 1 DNA in vitro. J Virol 1991, 65: 6942-6952.PubMedPubMedCentral Farnet CM, Haseltine WA: Circularization of human immunodeficiency virus type 1 DNA in vitro. J Virol 1991, 65: 6942-6952.PubMedPubMedCentral
5.
go back to reference Miller MD, Wang B, Bushman FD: Human immunodeficiency virus type 1 preintegration complexes containing discontinuous plus strands are competent to integrate in vitro. J Virol 1995, 69: 3938-3944.PubMedPubMedCentral Miller MD, Wang B, Bushman FD: Human immunodeficiency virus type 1 preintegration complexes containing discontinuous plus strands are competent to integrate in vitro. J Virol 1995, 69: 3938-3944.PubMedPubMedCentral
6.
go back to reference Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M: Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 1991, 254: 423-427.PubMedCrossRef Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M: Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 1991, 254: 423-427.PubMedCrossRef
7.
go back to reference Shoemaker C, Goff S, Gilboa E, Paskind M, Mitra SW, Baltimore D: Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. Proc Natl Acad Sci U S A 1980, 77: 3932-3936.PubMedPubMedCentralCrossRef Shoemaker C, Goff S, Gilboa E, Paskind M, Mitra SW, Baltimore D: Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. Proc Natl Acad Sci U S A 1980, 77: 3932-3936.PubMedPubMedCentralCrossRef
8.
go back to reference Mbisa JL, Barr R, Thomas JA, Vandegraaff N, Dorweiler IJ, Svarovskaia ES, Brown WL, Mansky LM, Gorelick RJ, Harris RS, et al.: Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. J Virol 2007, 81: 7099-7110.PubMedPubMedCentralCrossRef Mbisa JL, Barr R, Thomas JA, Vandegraaff N, Dorweiler IJ, Svarovskaia ES, Brown WL, Mansky LM, Gorelick RJ, Harris RS, et al.: Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. J Virol 2007, 81: 7099-7110.PubMedPubMedCentralCrossRef
9.
go back to reference Shaw GM, Hahn BH, Arya SK, Groopman JE, Gallo RC, Wong-Staal F: Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science 1984, 226: 1165-1171.PubMedCrossRef Shaw GM, Hahn BH, Arya SK, Groopman JE, Gallo RC, Wong-Staal F: Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science 1984, 226: 1165-1171.PubMedCrossRef
10.
go back to reference Luzuriaga K, McManus M, Catalina M, Mayack S, Sharkey M, Stevenson M, Sullivan JL: Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses. J Virol 2000, 74: 6984-6991.PubMedPubMedCentralCrossRef Luzuriaga K, McManus M, Catalina M, Mayack S, Sharkey M, Stevenson M, Sullivan JL: Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses. J Virol 2000, 74: 6984-6991.PubMedPubMedCentralCrossRef
11.
go back to reference Pang S, Koyanagi Y, Miles S, Wiley C, Vinters HV, Chen IS: High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature 1990, 343: 85-89.PubMedCrossRef Pang S, Koyanagi Y, Miles S, Wiley C, Vinters HV, Chen IS: High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature 1990, 343: 85-89.PubMedCrossRef
12.
go back to reference Teo I, Veryard C, Barnes H, An SF, Jones M, Lantos PL, Luthert P, Shaunak S: Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS. J Virol 1997, 71: 2928-2933.PubMedPubMedCentral Teo I, Veryard C, Barnes H, An SF, Jones M, Lantos PL, Luthert P, Shaunak S: Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS. J Virol 1997, 71: 2928-2933.PubMedPubMedCentral
13.
go back to reference Pierson TC, Kieffer TL, Ruff CT, Buck C, Gange SJ, Siliciano RF: Intrinsic stability of episomal circles formed during human immunodeficiency virus type 1 replication. J Virol 2002, 76: 4138-4144.PubMedPubMedCentralCrossRef Pierson TC, Kieffer TL, Ruff CT, Buck C, Gange SJ, Siliciano RF: Intrinsic stability of episomal circles formed during human immunodeficiency virus type 1 replication. J Virol 2002, 76: 4138-4144.PubMedPubMedCentralCrossRef
14.
go back to reference Butler SL, Johnson EP, Bushman FD: Human immunodeficiency virus cDNA metabolism: notable stability of two-long terminal repeat circles. J Virol 2002, 76: 3739-3747.PubMedPubMedCentralCrossRef Butler SL, Johnson EP, Bushman FD: Human immunodeficiency virus cDNA metabolism: notable stability of two-long terminal repeat circles. J Virol 2002, 76: 3739-3747.PubMedPubMedCentralCrossRef
15.
go back to reference Brussel A, Mathez D, Broche-Pierre S, Lancar R, Calvez T, Sonigo P, Leibowitch J: Longitudinal monitoring of 2-long terminal repeat circles in peripheral blood mononuclear cells from patients with chronic HIV-1 infection. AIDS 2003, 17: 645-652.PubMedCrossRef Brussel A, Mathez D, Broche-Pierre S, Lancar R, Calvez T, Sonigo P, Leibowitch J: Longitudinal monitoring of 2-long terminal repeat circles in peripheral blood mononuclear cells from patients with chronic HIV-1 infection. AIDS 2003, 17: 645-652.PubMedCrossRef
16.
go back to reference Cara A, Vargas J Jr, Keller M, Jones S, Mosoian A, Gurtman A, Cohen A, Parkas V, Wallach F, Chusid E, et al.: Circular viral DNA and anomalous junction sequence in PBMC of HIV-infected individuals with no detectable plasma HIV RNA. Virology 2002, 292: 1-5.PubMedCrossRef Cara A, Vargas J Jr, Keller M, Jones S, Mosoian A, Gurtman A, Cohen A, Parkas V, Wallach F, Chusid E, et al.: Circular viral DNA and anomalous junction sequence in PBMC of HIV-infected individuals with no detectable plasma HIV RNA. Virology 2002, 292: 1-5.PubMedCrossRef
17.
go back to reference Carr JM, Cheney KM, Coolen C, Davis A, Shaw D, Ferguson W, Chang G, Higgins G, Burrell C, Li P: Development of methods for coordinate measurement of total cell-associated and integrated human immunodeficiency virus type 1 (HIV-1) DNA forms in routine clinical samples: levels are not associated with clinical parameters, but low levels of integrated HIV-1 DNA may be prognostic for continued successful therapy. J Clin Microbiol 2007, 45: 1288-1297.PubMedPubMedCentralCrossRef Carr JM, Cheney KM, Coolen C, Davis A, Shaw D, Ferguson W, Chang G, Higgins G, Burrell C, Li P: Development of methods for coordinate measurement of total cell-associated and integrated human immunodeficiency virus type 1 (HIV-1) DNA forms in routine clinical samples: levels are not associated with clinical parameters, but low levels of integrated HIV-1 DNA may be prognostic for continued successful therapy. J Clin Microbiol 2007, 45: 1288-1297.PubMedPubMedCentralCrossRef
18.
go back to reference Sakai H, Kawamura M, Sakuragi J, Sakuragi S, Shibata R, Ishimoto A, Ono N, Ueda S, Adachi A: Integration is essential for efficient gene expression of human immunodeficiency virus type 1. J Virol 1993, 67: 1169-1174.PubMedPubMedCentral Sakai H, Kawamura M, Sakuragi J, Sakuragi S, Shibata R, Ishimoto A, Ono N, Ueda S, Adachi A: Integration is essential for efficient gene expression of human immunodeficiency virus type 1. J Virol 1993, 67: 1169-1174.PubMedPubMedCentral
19.
go back to reference Stevenson M, Haggerty S, Lamonica CA, Meier CM, Welch SK, Wasiak AJ: Integration is not necessary for expression of human immunodeficiency virus type 1 protein products. J Virol 1990, 64: 2421-2425.PubMedPubMedCentral Stevenson M, Haggerty S, Lamonica CA, Meier CM, Welch SK, Wasiak AJ: Integration is not necessary for expression of human immunodeficiency virus type 1 protein products. J Virol 1990, 64: 2421-2425.PubMedPubMedCentral
20.
go back to reference Wiskerchen M, Muesing MA: Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells. J Virol 1995, 69: 376-386.PubMedPubMedCentral Wiskerchen M, Muesing MA: Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells. J Virol 1995, 69: 376-386.PubMedPubMedCentral
21.
go back to reference Vandegraaff N, Kumar R, Burrell CJ, Li P: Kinetics of human immunodeficiency virus type 1 (HIV) DNA integration in acutely infected cells as determined using a novel assay for detection of integrated HIV DNA. J Virol 2001, 75: 11253-11260.PubMedPubMedCentralCrossRef Vandegraaff N, Kumar R, Burrell CJ, Li P: Kinetics of human immunodeficiency virus type 1 (HIV) DNA integration in acutely infected cells as determined using a novel assay for detection of integrated HIV DNA. J Virol 2001, 75: 11253-11260.PubMedPubMedCentralCrossRef
22.
go back to reference Robinson HL, Zinkus DM: Accumulation of human immunodeficiency virus type 1 DNA in T cells: results of multiple infection events. J Virol 1990, 64: 4836-4841.PubMedPubMedCentral Robinson HL, Zinkus DM: Accumulation of human immunodeficiency virus type 1 DNA in T cells: results of multiple infection events. J Virol 1990, 64: 4836-4841.PubMedPubMedCentral
23.
go back to reference Swiggard WJ, O'Doherty U, McGain D, Jeyakumar D, Malim MH: Long HIV type 1 reverse transcripts can accumulate stably within resting CD4+ T cells while short ones are degraded. AIDS Res Hum Retroviruses 2004, 20: 285-295.PubMedCrossRef Swiggard WJ, O'Doherty U, McGain D, Jeyakumar D, Malim MH: Long HIV type 1 reverse transcripts can accumulate stably within resting CD4+ T cells while short ones are degraded. AIDS Res Hum Retroviruses 2004, 20: 285-295.PubMedCrossRef
24.
go back to reference Wu Y, Marsh JW: Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA. Science 2001, 293: 1503-1506.PubMedCrossRef Wu Y, Marsh JW: Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA. Science 2001, 293: 1503-1506.PubMedCrossRef
25.
go back to reference Kantor B, Ma H, Webster-Cyriaque J, Monahan PE, Kafri T: Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain fatty acids and its implications for HIV infection. Proc Natl Acad Sci U S A 2009, 106: 18786-18791.PubMedPubMedCentralCrossRef Kantor B, Ma H, Webster-Cyriaque J, Monahan PE, Kafri T: Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain fatty acids and its implications for HIV infection. Proc Natl Acad Sci U S A 2009, 106: 18786-18791.PubMedPubMedCentralCrossRef
26.
go back to reference Gelderblom HC, Vatakis DN, Burke SA, Lawrie SD, Bristol GC, Levy DN: Viral complementation allows HIV-1 replication without integration. Retrovirology 2008, 5: 60.PubMedPubMedCentralCrossRef Gelderblom HC, Vatakis DN, Burke SA, Lawrie SD, Bristol GC, Levy DN: Viral complementation allows HIV-1 replication without integration. Retrovirology 2008, 5: 60.PubMedPubMedCentralCrossRef
27.
go back to reference Engelman A, Englund G, Orenstein JM, Martin MA, Craigie R: Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J Virol 1995, 69: 2729-2736.PubMedPubMedCentral Engelman A, Englund G, Orenstein JM, Martin MA, Craigie R: Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J Virol 1995, 69: 2729-2736.PubMedPubMedCentral
28.
go back to reference Kelly J, Beddall MH, Yu D, Iyer SR, Marsh JW, Wu Y: Human macrophages support persistent transcription from unintegrated HIV-1 DNA. Virology 2008, 372: 300-312.PubMedPubMedCentralCrossRef Kelly J, Beddall MH, Yu D, Iyer SR, Marsh JW, Wu Y: Human macrophages support persistent transcription from unintegrated HIV-1 DNA. Virology 2008, 372: 300-312.PubMedPubMedCentralCrossRef
29.
go back to reference Iyer SR, Yu D, Biancotto A, Margolis LB, Wu Y: Measurement of human immunodeficiency virus type 1 preintegration transcription by using Rev-dependent Rev-CEM cells reveals a sizable transcribing DNA population comparable to that from proviral templates. J Virol 2009, 83: 8662-8673.PubMedPubMedCentralCrossRef Iyer SR, Yu D, Biancotto A, Margolis LB, Wu Y: Measurement of human immunodeficiency virus type 1 preintegration transcription by using Rev-dependent Rev-CEM cells reveals a sizable transcribing DNA population comparable to that from proviral templates. J Virol 2009, 83: 8662-8673.PubMedPubMedCentralCrossRef
30.
31.
go back to reference Klimkait T, Strebel K, Hoggan MD, Martin MA, Orenstein JM: The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol 1990, 64: 621-629.PubMedPubMedCentral Klimkait T, Strebel K, Hoggan MD, Martin MA, Orenstein JM: The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol 1990, 64: 621-629.PubMedPubMedCentral
32.
go back to reference Bour S, Perrin C, Akari H, Strebel K: The human immunodeficiency virus type 1 Vpu protein inhibits NF-kappa B activation by interfering with beta TrCP-mediated degradation of Ikappa B. J Biol Chem 2001, 276: 15920-15928.PubMedCrossRef Bour S, Perrin C, Akari H, Strebel K: The human immunodeficiency virus type 1 Vpu protein inhibits NF-kappa B activation by interfering with beta TrCP-mediated degradation of Ikappa B. J Biol Chem 2001, 276: 15920-15928.PubMedCrossRef
33.
go back to reference Strebel K, Klimkait T, Maldarelli F, Martin MA: Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein. J Virol 1989, 63: 3784-3791.PubMedPubMedCentral Strebel K, Klimkait T, Maldarelli F, Martin MA: Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein. J Virol 1989, 63: 3784-3791.PubMedPubMedCentral
34.
go back to reference Hsu K, Seharaseyon J, Dong P, Bour S, Marban E: Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol Cell 2004, 14: 259-267.PubMedCrossRef Hsu K, Seharaseyon J, Dong P, Bour S, Marban E: Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol Cell 2004, 14: 259-267.PubMedCrossRef
35.
go back to reference Neil SJ, Zang T, Bieniasz PD: Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 2008, 451: 425-430.PubMedCrossRef Neil SJ, Zang T, Bieniasz PD: Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 2008, 451: 425-430.PubMedCrossRef
36.
go back to reference Czirjak G, Enyedi P: Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits. J Biol Chem 2002, 277: 5426-5432.PubMedCrossRef Czirjak G, Enyedi P: Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits. J Biol Chem 2002, 277: 5426-5432.PubMedCrossRef
37.
go back to reference Bolduan S, Votteler J, Lodermeyer V, Greiner T, Koppensteiner H, Schindler M, Thiel G, Schubert U: Ion channel activity of HIV-1 Vpu is dispensable for counteraction of CD317. Virology 2011, 416: 75-85.PubMedCrossRef Bolduan S, Votteler J, Lodermeyer V, Greiner T, Koppensteiner H, Schindler M, Thiel G, Schubert U: Ion channel activity of HIV-1 Vpu is dispensable for counteraction of CD317. Virology 2011, 416: 75-85.PubMedCrossRef
38.
go back to reference Ewart GD, Sutherland T, Gage PW, Cox GB: The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels. J Virol 1996, 70: 7108-7115.PubMedPubMedCentral Ewart GD, Sutherland T, Gage PW, Cox GB: The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels. J Virol 1996, 70: 7108-7115.PubMedPubMedCentral
39.
go back to reference Hegle AP, Marble DD, Wilson GF: A voltage-driven switch for ion-independent signaling by ether-a-go-go K+ channels. Proc Natl Acad Sci U S A 2006, 103: 2886-2891.PubMedPubMedCentralCrossRef Hegle AP, Marble DD, Wilson GF: A voltage-driven switch for ion-independent signaling by ether-a-go-go K+ channels. Proc Natl Acad Sci U S A 2006, 103: 2886-2891.PubMedPubMedCentralCrossRef
40.
go back to reference Ashmole I, Goodwin PA, Stanfield PR: TASK-5, a novel member of the tandem pore K+ channel family. Pflugers Arch 2001, 442: 828-833.PubMedCrossRef Ashmole I, Goodwin PA, Stanfield PR: TASK-5, a novel member of the tandem pore K+ channel family. Pflugers Arch 2001, 442: 828-833.PubMedCrossRef
42.
go back to reference Roux P, Alfieri C, Hrimech M, Cohen EA, Tanner JE: Activation of transcription factors NF-kappaB and NF-IL-6 by human immunodeficiency virus type 1 protein R (Vpr) induces interleukin-8 expression. J Virol 2000, 74: 4658-4665.PubMedPubMedCentralCrossRef Roux P, Alfieri C, Hrimech M, Cohen EA, Tanner JE: Activation of transcription factors NF-kappaB and NF-IL-6 by human immunodeficiency virus type 1 protein R (Vpr) induces interleukin-8 expression. J Virol 2000, 74: 4658-4665.PubMedPubMedCentralCrossRef
43.
go back to reference Felzien LK, Woffendin C, Hottiger MO, Subbramanian RA, Cohen EA, Nabel GJ: HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator. Proc Natl Acad Sci U S A 1998, 95: 5281-5286.PubMedPubMedCentralCrossRef Felzien LK, Woffendin C, Hottiger MO, Subbramanian RA, Cohen EA, Nabel GJ: HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator. Proc Natl Acad Sci U S A 1998, 95: 5281-5286.PubMedPubMedCentralCrossRef
44.
go back to reference Demarchi F, Gutierrez MI, Giacca M: Human immunodeficiency virus type 1 tat protein activates transcription factor NF-kappaB through the cellular interferon-inducible, double-stranded RNA-dependent protein kinase, PKR. J Virol 1999, 73: 7080-7086.PubMedPubMedCentral Demarchi F, Gutierrez MI, Giacca M: Human immunodeficiency virus type 1 tat protein activates transcription factor NF-kappaB through the cellular interferon-inducible, double-stranded RNA-dependent protein kinase, PKR. J Virol 1999, 73: 7080-7086.PubMedPubMedCentral
45.
go back to reference Clouse KA, Cosentino LM, Weih KA, Pyle SW, Robbins PB, Hochstein HD, Natarajan V, Farrar WL: The HIV-1 gp120 envelope protein has the intrinsic capacity to stimulate monokine secretion. J Immunol 1991, 147: 2892-2901.PubMed Clouse KA, Cosentino LM, Weih KA, Pyle SW, Robbins PB, Hochstein HD, Natarajan V, Farrar WL: The HIV-1 gp120 envelope protein has the intrinsic capacity to stimulate monokine secretion. J Immunol 1991, 147: 2892-2901.PubMed
46.
go back to reference Hofman FM, Wright AD, Dohadwala MM, Wong-Staal F, Walker SM: Exogenous tat protein activates human endothelial cells. Blood 1993, 82: 2774-2780.PubMed Hofman FM, Wright AD, Dohadwala MM, Wong-Staal F, Walker SM: Exogenous tat protein activates human endothelial cells. Blood 1993, 82: 2774-2780.PubMed
47.
go back to reference DeLuca C, Roulston A, Koromilas A, Wainberg MA, Hiscott J: Chronic human immunodeficiency virus type 1 infection of myeloid cells disrupts the autoregulatory control of the NF-kappaB/Rel pathway via enhanced IkappaBalpha degradation. J Virol 1996, 70: 5183-5193.PubMedPubMedCentral DeLuca C, Roulston A, Koromilas A, Wainberg MA, Hiscott J: Chronic human immunodeficiency virus type 1 infection of myeloid cells disrupts the autoregulatory control of the NF-kappaB/Rel pathway via enhanced IkappaBalpha degradation. J Virol 1996, 70: 5183-5193.PubMedPubMedCentral
48.
go back to reference Asin S, Taylor JA, Trushin S, Bren G, Paya CV: Ikappakappa mediates NF-kappaB activation in human immunodeficiency virus-infected cells. J Virol 1999, 73: 3893-3903.PubMedPubMedCentral Asin S, Taylor JA, Trushin S, Bren G, Paya CV: Ikappakappa mediates NF-kappaB activation in human immunodeficiency virus-infected cells. J Virol 1999, 73: 3893-3903.PubMedPubMedCentral
49.
go back to reference DeLuca C, Petropoulos L, Zmeureanu D, Hiscott J: Nuclear IkappaBbeta maintains persistent NF-kappaB activation in HIV-1-infected myeloid cells. J Biol Chem 1999, 274: 13010-13016.PubMedCrossRef DeLuca C, Petropoulos L, Zmeureanu D, Hiscott J: Nuclear IkappaBbeta maintains persistent NF-kappaB activation in HIV-1-infected myeloid cells. J Biol Chem 1999, 274: 13010-13016.PubMedCrossRef
50.
go back to reference Meuth SG, Bittner S, Meuth P, Simon OJ, Budde T, Wiendl H: TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions. J Biol Chem 2008, 283: 14559-14570.PubMedCrossRef Meuth SG, Bittner S, Meuth P, Simon OJ, Budde T, Wiendl H: TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions. J Biol Chem 2008, 283: 14559-14570.PubMedCrossRef
51.
go back to reference Cara A, Guarnaccia F, Reitz MS, Gallo RC, Lori F: Self-limiting, cell type-dependent replication of an integrase-defective human immunodeficiency virus type 1 in human primary macrophages but not T lymphocytes. Virology 1995, 208: 242-248.PubMedCrossRef Cara A, Guarnaccia F, Reitz MS, Gallo RC, Lori F: Self-limiting, cell type-dependent replication of an integrase-defective human immunodeficiency virus type 1 in human primary macrophages but not T lymphocytes. Virology 1995, 208: 242-248.PubMedCrossRef
52.
go back to reference Lu R, Nakajima N, Hofmann W, Benkirane M, Jeang KT, Sodroski J, Engelman A: Simian virus 40-based replication of catalytically inactive human immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and monocyte-derived macrophages. J Virol 2004, 78: 658-668.PubMedPubMedCentralCrossRef Lu R, Nakajima N, Hofmann W, Benkirane M, Jeang KT, Sodroski J, Engelman A: Simian virus 40-based replication of catalytically inactive human immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and monocyte-derived macrophages. J Virol 2004, 78: 658-668.PubMedPubMedCentralCrossRef
53.
go back to reference Nakajima N, Lu R, Engelman A: Human immunodeficiency virus type 1 replication in the absence of integrase-mediated dna recombination: definition of permissive and nonpermissive T-cell lines. J Virol 2001, 75: 7944-7955.PubMedPubMedCentralCrossRef Nakajima N, Lu R, Engelman A: Human immunodeficiency virus type 1 replication in the absence of integrase-mediated dna recombination: definition of permissive and nonpermissive T-cell lines. J Virol 2001, 75: 7944-7955.PubMedPubMedCentralCrossRef
54.
go back to reference Stevenson M, Stanwick TL, Dempsey MP, Lamonica CA: HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J 1990, 9: 1551-1560.PubMedPubMedCentral Stevenson M, Stanwick TL, Dempsey MP, Lamonica CA: HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J 1990, 9: 1551-1560.PubMedPubMedCentral
55.
go back to reference Kilzer JM, Stracker T, Beitzel B, Meek K, Weitzman M, Bushman FD: Roles of host cell factors in circularization of retroviral dna. Virology 2003, 314: 460-467.PubMedCrossRef Kilzer JM, Stracker T, Beitzel B, Meek K, Weitzman M, Bushman FD: Roles of host cell factors in circularization of retroviral dna. Virology 2003, 314: 460-467.PubMedCrossRef
56.
go back to reference Zheng Y, Ao Z, Wang B, Jayappa KD, Yao X: Host protein Ku70 binds and protects HIV-1 integrase from proteasomal degradation and is required for HIV replication. J Biol Chem 2011, 286: 17722-17735.PubMedPubMedCentralCrossRef Zheng Y, Ao Z, Wang B, Jayappa KD, Yao X: Host protein Ku70 binds and protects HIV-1 integrase from proteasomal degradation and is required for HIV replication. J Biol Chem 2011, 286: 17722-17735.PubMedPubMedCentralCrossRef
57.
go back to reference Michel N, Allespach I, Venzke S, Fackler OT, Keppler OT: The Nef protein of human immunodeficiency virus establishes superinfection immunity by a dual strategy to downregulate cell-surface CCR5 and CD4. Curr Biol 2005, 15: 714-723.PubMedCrossRef Michel N, Allespach I, Venzke S, Fackler OT, Keppler OT: The Nef protein of human immunodeficiency virus establishes superinfection immunity by a dual strategy to downregulate cell-surface CCR5 and CD4. Curr Biol 2005, 15: 714-723.PubMedCrossRef
58.
go back to reference Venzke S, Michel N, Allespach I, Fackler OT, Keppler OT: Expression of Nef downregulates CXCR4, the major coreceptor of human immunodeficiency virus, from the surfaces of target cells and thereby enhances resistance to superinfection. J Virol 2006, 80: 11141-11152.PubMedPubMedCentralCrossRef Venzke S, Michel N, Allespach I, Fackler OT, Keppler OT: Expression of Nef downregulates CXCR4, the major coreceptor of human immunodeficiency virus, from the surfaces of target cells and thereby enhances resistance to superinfection. J Virol 2006, 80: 11141-11152.PubMedPubMedCentralCrossRef
59.
go back to reference Wildum S, Schindler M, Munch J, Kirchhoff F: Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. J Virol 2006, 80: 8047-8059.PubMedPubMedCentralCrossRef Wildum S, Schindler M, Munch J, Kirchhoff F: Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. J Virol 2006, 80: 8047-8059.PubMedPubMedCentralCrossRef
60.
go back to reference Sloan RD, Donahue DA, Kuhl BD, Bar-Magen T, Wainberg MA: Expression of Nef from unintegrated HIV-1 DNA downregulates cell surface CXCR4 and CCR5 on T-lymphocytes. Retrovirology 2010, 7: 44.PubMedPubMedCentralCrossRef Sloan RD, Donahue DA, Kuhl BD, Bar-Magen T, Wainberg MA: Expression of Nef from unintegrated HIV-1 DNA downregulates cell surface CXCR4 and CCR5 on T-lymphocytes. Retrovirology 2010, 7: 44.PubMedPubMedCentralCrossRef
61.
go back to reference Sloan RD, Kuhl BD, Donahue DA, Roland A, Bar-Magen T, Wainberg MA: Transcription of preintegrated HIV-1 cDNA modulates cell surface expression of major histocompatibility complex class I via Nef. J Virol 2011, 85: 2828-2836.PubMedPubMedCentralCrossRef Sloan RD, Kuhl BD, Donahue DA, Roland A, Bar-Magen T, Wainberg MA: Transcription of preintegrated HIV-1 cDNA modulates cell surface expression of major histocompatibility complex class I via Nef. J Virol 2011, 85: 2828-2836.PubMedPubMedCentralCrossRef
62.
go back to reference Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, Strominger JL, Baltimore D: The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 1999, 10: 661-671.PubMedCrossRef Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, Strominger JL, Baltimore D: The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 1999, 10: 661-671.PubMedCrossRef
63.
go back to reference Collins KL, Chen BK, Kalams SA, Walker BD, Baltimore D: HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 1998, 391: 397-401.PubMedCrossRef Collins KL, Chen BK, Kalams SA, Walker BD, Baltimore D: HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 1998, 391: 397-401.PubMedCrossRef
64.
go back to reference Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P: Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995, 270: 1811-1815.PubMedCrossRef Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P: Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995, 270: 1811-1815.PubMedCrossRef
65.
go back to reference Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM: Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 1996, 2: 338-342.PubMedCrossRef Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM: Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 1996, 2: 338-342.PubMedCrossRef
66.
go back to reference Yanez-Munoz RJ, Balaggan KS, MacNeil A, Howe SJ, Schmidt M, Smith AJ, Buch P, MacLaren RE, Anderson PN, Barker SE, et al.: Effective gene therapy with nonintegrating lentiviral vectors. Nat Med 2006, 12: 348-353.PubMedCrossRef Yanez-Munoz RJ, Balaggan KS, MacNeil A, Howe SJ, Schmidt M, Smith AJ, Buch P, MacLaren RE, Anderson PN, Barker SE, et al.: Effective gene therapy with nonintegrating lentiviral vectors. Nat Med 2006, 12: 348-353.PubMedCrossRef
67.
go back to reference Philippe S, Sarkis C, Barkats M, Mammeri H, Ladroue C, Petit C, Mallet J, Serguera C: Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo. Proc Natl Acad Sci U S A 2006, 103: 17684-17689.PubMedPubMedCentralCrossRef Philippe S, Sarkis C, Barkats M, Mammeri H, Ladroue C, Petit C, Mallet J, Serguera C: Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo. Proc Natl Acad Sci U S A 2006, 103: 17684-17689.PubMedPubMedCentralCrossRef
69.
go back to reference Berg AP, Talley EM, Manger JP, Bayliss DA: Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. J Neurosci 2004, 24: 6693-6702.PubMedCrossRef Berg AP, Talley EM, Manger JP, Bayliss DA: Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. J Neurosci 2004, 24: 6693-6702.PubMedCrossRef
70.
go back to reference Dowling D, Nasr-Esfahani S, Tan CH, O'Brien K, Howard JL, Jans DA, Purcell DF, Stoltzfus CM, Sonza S: HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages. Retrovirology 2008, 5: 18.PubMedPubMedCentralCrossRef Dowling D, Nasr-Esfahani S, Tan CH, O'Brien K, Howard JL, Jans DA, Purcell DF, Stoltzfus CM, Sonza S: HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages. Retrovirology 2008, 5: 18.PubMedPubMedCentralCrossRef
Metadata
Title
Human immunodeficiency virus type 1 Vpu and cellular TASK proteins suppress transcription of unintegrated HIV-1 DNA
Authors
Nkiruka Emeagwali
James EK Hildreth
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2012
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-9-277

Other articles of this Issue 1/2012

Virology Journal 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.