scholarly journals The Conserved Glycine-Rich Segment Linking the N-Terminal Fusion Peptide to the Coiled Coil of Human T-Cell Leukemia Virus Type 1 Transmembrane Glycoprotein gp21 Is a Determinant of Membrane Fusion Function

2005 ◽  
Vol 79 (7) ◽  
pp. 4533-4539 ◽  
Author(s):  
Kirilee A. Wilson ◽  
Séverine Bär ◽  
Anne L. Maerz ◽  
Marc Alizon ◽  
Pantelis Poumbourios
Keyword(s):  
T Cell ◽  
Membrane Fusion ◽  
Leukemia Virus ◽  
Coiled Coil ◽  
Fusion Peptide ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Retroviral transmembrane proteins (TMs) contain an N-terminal fusion peptide that initiates virus-cell membrane fusion. The fusion peptide is linked to the coiled-coil core through a conserved sequence that is often rich in glycines. We investigated the functional role of the glycine-rich segment, Met-326 to Ser-337, of the human T-cell leukemia virus type 1 (HTLV-1) TM, gp21, by alanine and proline scanning mutagenesis. Alanine substitution for the hydrophobic residue Ile-334 caused an ∼90% reduction in cell-cell fusion activity without detectable effects on the lipid-mixing and pore formation phases of fusion. Alanine substitutions at other positions had smaller effects (Gly-329, Val-330, and Gly-332) or no effect on fusion function. Proline substitution for glycine residues inhibited cell-cell fusion function with position-dependent effects on the three phases of fusion. Retroviral glycoprotein fusion function thus appears to require flexibility within the glycine-rich segment and hydrophobic contacts mediated by this segment.

scholarly journals The Synthetic Peptide P-197 Inhibits Human T-Cell Leukemia Virus Type 1 Envelope-Mediated Syncytium Formation by a Mechanism That Is Independent of Hsc70

2001 ◽  
Vol 75 (21) ◽  
pp. 10472-10478 ◽  
Author(s):  
David W. Brighty ◽  
Sushma R. Jassal
Keyword(s):  
T Cell ◽  
Membrane Fusion ◽  
Synthetic Peptide ◽  
Leukemia Virus ◽  
Target Cells ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Entry of human T-cell leukemia virus type 1 (HTLV-1) into cells is mediated by the viral envelope glycoproteins gp46 and gp21. The gp46 surface glycoprotein binds to a poorly characterized cell surface receptor, thereby promoting the gp21-dependent fusion of the viral and cellular membranes. Interestingly, a synthetic peptide (P-197) simulating amino acids 197 to 216 of gp46 strongly inhibits envelope-dependent membrane fusion with Molt-4 target cells. It has been suggested that this peptide acts by competitively binding to Hsc70, a putative cellular receptor for HTLV-1. We now demonstrate that P-197 inhibits membrane fusion among diverse HTLV-1-permissive target cells. Importantly, most of these cells lack detectable levels of Hsc70, indicating that P-197 inhibits membrane fusion by a mechanism that is Hsc70 independent. We now suggest that competition for primary receptor binding is unlikely to account for the inhibitory activity of P-197. Understanding the mechanism by which P-197 functions may reveal concepts of general relevance to antiretroviral chemotherapy.

scholarly journals An Antiviral Peptide Targets a Coiled-Coil Domain of the Human T-Cell Leukemia Virus Envelope Glycoprotein

2003 ◽  
Vol 77 (5) ◽  
pp. 3281-3290 ◽  
Author(s):  
Josefina D. Piñón ◽  
Sharon M. Kelly ◽  
Nicholas C. Price ◽  
Jack U. Flanagan ◽  
David W. Brighty
Keyword(s):  
T Cell ◽  
Membrane Fusion ◽  
Leukemia Virus ◽  
Coiled Coil ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Coiled Coil Domain ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Retrovirus entry into cells is mediated by the viral envelope glycoproteins which, through a cascade of conformational changes, orchestrate fusion of the viral and cellular membranes. In the absence of membrane fusion, viral entry into the host cell cannot occur. For human T-cell leukemia virus type 1 (HTLV-1), synthetic peptides that mimic a carboxy-terminal region of the transmembrane glycoprotein (TM) ectodomain are potent inhibitors of membrane fusion and virus entry. Here, we demonstrate that this class of inhibitor targets a fusion-active structure of HTLV-1 envelope. In particular, the peptides bind specifically to a core coiled-coil domain of envelope, and peptide variants that fail to bind the coiled-coil lack inhibitory activity. Our data indicate that the inhibitory peptides likely function by disrupting the formation of a trimer-of-hairpins structure that is required for membrane fusion. Importantly, we also show that peptides exhibiting dramatically increased potency can be readily obtained. We suggest that peptides or peptide mimetics targeting the fusion-active structures of envelope may be of therapeutic value in the treatment of HTLV-1 infections.

scholarly journals Smoking is a risk factor for development of adult T-cell leukemia/lymphoma in Japanese human T-cell leukemia virus type-1 carriers

2016 ◽  
Vol 27 (9) ◽  
pp. 1059-1066 ◽  
Author(s):  
Hisayoshi Kondo ◽  
Midori Soda ◽  
Norie Sawada ◽  
Manami Inoue ◽  
Yoshitaka Imaizumi ◽  
...  
Keyword(s):  
Risk Factor ◽  
T Cell ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results

2017 ◽  
Vol 55 (9) ◽  
pp. 2838-2849 ◽  
Author(s):  
Madoka Kuramitsu ◽  
Tsuyoshi Sekizuka ◽  
Tadanori Yamochi ◽  
Sanaz Firouzi ◽  
Tomoo Sato ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Proviral Load ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACTWestern blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%), and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens because of a combination of a low proviral load and mutations in the provirus, which may interfere with host recognition of HTLV-1 antigens.

Prevalence of Antibody to Human T Cell Leukemia Virus Type 1 (HTLV-I) in Populations of Ivory Coast, West Africa

1989 ◽  
Vol 160 (3) ◽  
pp. 363-370 ◽  
Author(s):  
M. Verdier ◽  
F. Denis ◽  
A. Sangare ◽  
F. Barin ◽  
G. Gershy-Damet ◽  
...  
Keyword(s):  
T Cell ◽  
West Africa ◽  
Virus Type ◽  
Ivory Coast ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Human T-cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1

Oncogene ◽  
2004 ◽  
Vol 23 (29) ◽  
pp. 4966-4974 ◽  
Author(s):  
Hyeon Ung Park ◽  
Jae-Hoon Jeong ◽  
Jay H Chung ◽  
John N Brady
Keyword(s):  
Dna Damage ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
G2 Arrest ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Human T Cell Leukemia Virus Type 1 Tax Inhibits Innate Antiviral Signaling via NF- B-Dependent Induction of SOCS1

2011 ◽  
Vol 85 (14) ◽  
pp. 6955-6962 ◽  
Author(s):  
S. Charoenthongtrakul ◽  
Q. Zhou ◽  
N. Shembade ◽  
N. S. Harhaj ◽  
E. W. Harhaj
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Antiviral Signaling ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus
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