Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome.

Matsuda, Zene; Chou, Min-Ji; Matsuda, Michiko; Huang, Jingsheng; Chen, Yiming; Redfield, Robert; Mayer, Kenneth H.; Essex, Max; Lee, Tun‐Hou

doi:10.1073/pnas.85.18.6968

Cited by 73 publications

(34 citation statements)

References 42 publications

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“…§1734 solely to indicate this fact. 3 and then centrifuged at 35,000 ϫ g for 30 min. The resulting pellet was sonicated twice for 4 min on ice in binding buffer (6 M guanidine hydrochloride͞5 mM imidazole͞0.5 M NaCl͞20 mM Tris-Cl, pH 8.0).…”

Section: Methodsmentioning

confidence: 99%

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Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1

Marassi

Gratkowski

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

155

221

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Vpu is an 81-residue membrane protein encoded by the HIV-1 genome. NMR experiments show that the protein folds into two distinct domains, a transmembrane hydrophobic helix and a cytoplasmic domain with two in-plane amphipathic ␣-helices separated by a linker region. Resonances in one-dimensional solid-state NMR spectra of uniformly 15 N labeled Vpu are clearly segregated into two bands at chemical shift frequencies associated with NH bonds in a transmembrane ␣-helix, perpendicular to the membrane surface, and with NH bonds in the cytoplasmic helices parallel to the membrane surface. Solid-state NMR spectra of truncated Vpu 2-51 (residues 2-51), which contains the transmembrane ␣-helix and the first amphipathic helix of the cytoplasmic domain, and of a construct Vpu 28 -81 (residues 28 -81), which contains only the cytoplasmic domain, support this structural model of Vpu in the membrane. Full-length Vpu (residues 2-81) forms discrete ion-conducting channels of heterogeneous conductance in lipid bilayers. The most frequent conductances were 22 ؎ 3 pS and 12 ؎ 3 pS in 0.5 M KCl and 29 ؎ 3 pS and 12 ؎ 3 pS in 0.5 M NaCl. In agreement with the structural model, truncated Vpu 2-51, which has the transmembrane helix, forms discrete channels in lipid bilayers, whereas the cytoplasmic domain Vpu 28 -81, which lacks the transmembrane helix, does not. This finding shows that the channel activity is associated with the transmembrane helical domain. The pattern of channel activity is characteristic of the self-assembly of conductive oligomers in the membrane and is compatible with the structural and functional findings.

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Section: Methodsmentioning

confidence: 99%

“…Vpu, one of four accessory proteins encoded in the HIV-1 genome, is an 81-residue membrane protein (1)(2)(3). A growing body of evidence from biological, functional, and structural studies indicates that its two principal biological activities are associated with different structural domains of the protein (4).…”

mentioning

confidence: 99%

Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1

Marassi

Gratkowski

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

155

221

View full text Add to dashboard Cite

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“…[1][2][3] Studies in a macaque model have shown that Vpu from subtype B plays a crucial role in massive loss of circulating CD4 ϩ T lymphocytes, 4-6 which can be modulated by replacing it with Vpu from subtype C. 7 The exact mechanism(s) underlying how Vpu makes HIV-1 more pathogenic is only partially understood. 8,9 Vpu is involved in ubiquitination and degradation of antiretroviral restriction factor BM stromal cell Ag 2 (BST-2; also known as tetherin) and surface receptor CD4 through their recruitment to SCF ␤-TrcP (Skp1/Cul1/F-box) ubiquitin ligase (SCF) complex.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of β-TrcP–dependent ubiquitination of p53 by HIV-1 Vpu promotes p53–mediated apoptosis in human T cells

Verma

Ali

Arora

et al. 2011

Blood

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IntroductionHIV type 1 (HIV-1) Vpu (viral protein U) is an accessory gene exclusive to HIV-1 but not present in HIV-2 and in most SIVs. [1][2][3] Studies in a macaque model have shown that Vpu from subtype B plays a crucial role in massive loss of circulating CD4 ϩ T lymphocytes, 4-6 which can be modulated by replacing it with Vpu from subtype C. 7 The exact mechanism(s) underlying how Vpu makes HIV-1 more pathogenic is only partially understood. 8,9 Vpu is involved in ubiquitination and degradation of antiretroviral restriction factor BM stromal cell Ag 2 (BST-2; also known as tetherin) and surface receptor CD4 through their recruitment to SCF ␤-TrcP (Skp1/Cul1/F-box) ubiquitin ligase (SCF) complex. [10][11][12][13] The key to biologic function of Vpu is the presence of a highly conserved 6-amino acid (DS 52 GNES 56 ) sequence that constitutes the ␤-TrcP (␤-transducin repeat-containing proteins) binding motif. 14 This motif is constitutively phosphorylated and mediates interaction of Vpu with ␤-TrcP, the substrate recognition subunit of SCF ␤-TrcP complex. Hence, Vpu acts as an adaptor linking its target proteins (CD4 and BST-2) to a host E3 ubiquitin ligase SCF ␤-TrcP complex, which are otherwise not the natural substrates of this complex. However, unlike natural substrates of ␤-TrcP, which are targeted for degradation, Vpu itself is resistant to degradation and can form stable complexes with ␤-TrcP. 15 Thus, expression of constitutively phosphorylated Vpu in infected cells leads to competitive inhibition of ubiquitination and subsequent proteosomal degradation of many natural substrates of SCF ␤-TrcP complex (␤-catenin, activating transcription factor 4, and I␤-␣) and results in changes in the profile of cellular proteins that may contribute to cytopathic effects during HIV-1 infection. 9,15,16 The inability to degrade I␤-␣ and to activate NF-␤ on stimulation with TNF-␣ explains the TNF-␣-sensitive phenotype of Vpu-expressing cells. 9 Interestingly, more recent data suggest that Vpu is also degraded by both ␤-TrcPdependent 17 and -independent pathways, 18 which in turn may have a role in modulating biologic activities of Vpu.The SCF ␤-TrcP ubiquitin ligase complex controls the functions of a wide spectrum of cellular proteins 16,[19][20][21][22] ; many of them are involved in pathways crucial to HIV-1 pathology. Tumor suppressor protein p53 is reported to be a major player involved in HIV-1-induced apoptosis. [23][24][25] p53 protein has been shown to be an important substrate of ␤-TrcP-dependent ubiquitination. Small interfering RNA (siRNA)-mediated depletion of components of SCF ␤-TrcP complex or the expression of a dominant-negative form of ␤-TrcP was shown to enhance the stability of p53 protein and also to activate p53 downstream signaling events. 22 Like most of the natural ␤-TrcP substrates (I␤-␣, ␤-catenin, p65, and steroid receptor coactivator 3), the I␤ kinase 2 (IKK2/IKK␤) also phosphorylates p53 at serine 362/366 (Ser362/366) position directing it for ␤-TrcP-mediated ubiquitination in an Mdm-2 ind...

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“…Aside from the typical retroviral gag, pol, and env genes, HIV encodes a series of accessory genes, vif, vpr, vpx, vpu, and ne$ The vpu gene is found exclusively in HIV-1 (Strebel et al, 1988;Cohen et al, 1988;Matsuda, 1988). In tissue culture systems, defects in accessory genes are frequently not correlated with a detectable impairment of virus replication and, as a result, these genes are often referred to as "non-essential".…”

Section: Introductionmentioning

confidence: 99%

Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

Myers¹,

Foley²,

Korber

et al. 1997

366

678

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Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome.

Abstract: Eight coding regions designated gag,pol, env, sor, R

Cited by 73 publications

References 42 publications

Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1

Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1

Inhibition of β-TrcP–dependent ubiquitination of p53 by HIV-1 Vpu promotes p53–mediated apoptosis in human T cells

Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

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