Blockade of human immunodeficiency virus type 1 production in CD4+ T cells by an intracellular CD4 expressed under control of the viral long terminal repeat.
Proceedings of the National Academy of SciencesPublished 1 April 1993Open access
Linda Buonocore, J K Rose
Citations51
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
There was a complete block to maturation of infectious HIV-1 in the transduced cells, no viral spread, and little or no syncytium formation, and this intracellular trap for HIV has potential application in gene therapy for AIDS.
Abstract
A retroviral vector was constructed in which a gene encoding a mutated soluble CD4 protein that is retained in the endoplasmic reticulum (sCD4-KDEL) is expressed under control of human immunodeficiency virus type 1 (HIV-1) regulatory elements. HIV-1 infection of a human T-cell line transduced with this vector led to induction of sCD4-KDEL synthesis and a block in transport of the HIV envelope protein to the cell surface. There was a complete block to maturation of infectious HIV-1 in the transduced cells, no viral spread, and little or no syncytium formation. Infected cells gradually disappeared from the culture over a period of 2 months. This intracellular trap for HIV has potential application in gene therapy for AIDS.
Keywords
Immunology and MicrobiologyMedicine
NatureCleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
251,640 Citations1970Ulrich K. Laemmli
Using an improved method of gel electrophoresis, many hitherto unknown proteins have been found in bacteriophage T4 and some of these have been identified with specific gene products.
Cellular Physiology and BiochemistryShort-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues
47,283 Citations2013Haider Raza, Annie John +1 more
The results suggest that even short term exposure of cigarette smoke have adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking.
Journal of Histochemistry & CytochemistryPERIODATE-LYSINE-PARAFORMALDEHYDE FIXATIVE A NEW FIXATIVE FOR IMMUNOELECTRON MICROSCOPY
3,824 Citations1974Ian W. McLean, Paul K. Nakane
Using this fixative and the peroxidase-labeled antibody technique, basement membrane antigen was localized within the cisternae of endoplasmic reticulum of parietal yolk sac cells and in extracellular basement membranes with adequate tissue preservation, a task which has not been successfully accomplished by conventional fixatives.
ScienceDetection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS
3,544 Citations1984Mikuláš Popovič, M. G. Sarngadharan +2 more
A cell system was developed for the reproducible detection of human T-lymphotropic retroviruses (HTLV family) from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS), and it provides large amounts of virus for detailed molecular and immunological analyses.
CellA C-terminal signal prevents secretion of luminal ER proteins
2,214 Citations1987Sean Munro, Hugh R.B. Pelham
It is proposed that the KDEL sequence marks proteins that are to be retained in the ER and discuss possible retention mechanisms.
CellThe T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain
1,998 Citations1986Paul J. Maddon, Angus Dalgleish +4 more
The studies support a mechanism of AIDS virus infection that initially involves the specific interaction of theAIDS virus with T4 molecules on the cell surface, and find that the T4 gene is expressed in the brain as well as in lymphoid cells, providing an explanation for the dual neurotropic and lymphotropic character of the AIDS virus.
PubMedImproved retroviral vectors for gene transfer and expression.
1,991 Citations1989A. Dusty Miller, G J Rosman
A set of murine retrovirus-based vectors that include unique cloning sites for insertion of cDNAs such that the cDNA can be driven by either the retroviral long terminal repeat, the immediate early promoter of human cytomegalovirus, or the simian virus 40 early promoter are described.
Molecular and Cellular BiologyRedesign of Retrovirus Packaging Cell Lines To Avoid Recombination Leading to Helper Virus Production
1,255 Citations1986A. Dusty Miller, Carol Buttimore
It is shown that the ability to package virus is conferred at very low frequency to cells infected with virus from these retrovirus packaging cell lines, presumably by low-frequency transmission of the deleted virus genome.
NatureRole of the HTLV-III/LAV envelope in syncytium formation and cytopathicity
800 Citations1986Joseph Sodroski, Wei Chun Goh +3 more
The basis for the specific cytotoxicity of the virus is investigated, and it is reported that high-level expression of the HTLV-III envelope gene induces syncytia and concomitant cell death in T4+ cell lines but not in a B-lymphocyte line.
CellFunctional dissection of the HIV-1 Rev trans-activator—Derivation of a trans-dominant repressor of Rev function
734 Citations1989Michael H. Malim, S Böhnlein +2 more
Mutation of a second, more C-terminal Rev protein sequence element was found to yield defective Rev proteins that act as trans-dominant inhibitors of Rev function, and these Rev mutants are shown to inhibit HIV-1 replication when expressed in transfected cells and may have potential application in the treatment of AIDS related disease.
CellThe isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family
664 Citations1985Paul J. Maddon, Dan R. Littman +4 more
Comparison of the protein sequences deduced from the T4 and T8 cDNAs reveals structural similarities consistent with their postulated role as recognition molecules, as well as differences suggesting that the two proteins recognize different structures on the target cell.
ScienceRibozymes as Potential Anti-HIV-1 Therapeutic Agents
663 Citations1990Nava Sarver, Edouard M. Cantin +5 more
The present study shows precise cleavage of human immunodeficiency virus type 1 (HIV-1) sequences in a cell-free system by hammerhead ribozymes, suggesting the feasibility of developing Ribozymes as therapeutic agents against human pathogens such as HIV-1.
CellRegulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein
661 Citations1987Mark A. Muesing
It is shown that the trans-activator is the protein product of the tat gene, identified biochemically in HIV-infected and transfected cells as an Mr 15,000 polypeptide, and possible mechanisms whereby the interaction of p15tat with the dyad element promotes the accumulation of LTR-directed mRNA.
ScienceMolecular Characterization of Human T-Cell Leukemia (Lymphotropic) Virus Type III in the Acquired Immune Deficiency Syndrome
631 Citations1984George M. Shaw, Beatrice H. Hahn +4 more
The results revealed that HTLV-III is an exogenous human retrovirus that lacks nucleic acid sequences derived from normal human DNA and can be detected in low levels in fresh lymphoid tissue of a minority of patients with AIDS or ARC but appears not to be present in Kaposi's sarcoma tissue.
NatureInduction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein
591 Citations1986Jeffrey D. Lifson, Mark B. Feinberg +8 more
It is demonstrated that cell-surface expression of this protein, in the absence of other HTLV-III/LAV structural or regulatory proteins, is sufficient to induce CD4-dependent cell fusion, leading to cell death, one of the characteristic manifestations of AIDS (acquired immune deficiency syndrome) virus cytopathology.
ScienceAIDS Retrovirus Induced Cytopathology: Giant Cell Formation and Involvement of CD4 antigen
520 Citations1986Jeffrey D. Lifson, Gregory R. Reyes +3 more
It is suggested that, in vivo, cell fusion involving the CD4 molecule may represent a mechanism whereby uninfected cells can be incorporated into AIDS virus infected syncytia.
Science<i>Trans</i> -Acting Transcriptional Regulation of Human T-Cell Leukemia Virus Type III Long Terminal Repeat
499 Citations1985Joseph Sodroski, C A Rosen +6 more
It is shown that, in human T-cell lines infected with HTLV-III, gene expression directed by the long terminal repeat sequence of this virus is stimulated by more than two orders of magnitude compared to matched uninfected cells.
CellOverexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication
444 Citations1990Bruce A. Sullenger, Humilidad F. Gallardo +2 more
TAR decoy RNA-mediated HIV inhibition may also be effective against natural HIV isolates in spite of their hypervariable nature, as suggested by the fact that replication of SIVmac was also inhibited in cells expressing HIV-1 TAR decoys.
BloodMitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas
423 Citations1980AF Gazdar, DN Carney +5 more
CTCL cells were more resistant to the toxic effects ofMitogens than lymphocytes from normal donors, permitting the use of mitogens as long-term growth factors, and have proliferated without mitogens for over a year.
The Journal of Cell BiologyA quantitative analysis of the endocytic pathway in baby hamster kidney cells.
320 Citations1989Gareth Griffiths, R Back +1 more
The stereological values given in the present study, in combination with earlier studies, provide a minimum estimate for both the total surface area of membranes and the rate of membrane synthesis in a BHK cell.
CellHIV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus
296 Citations1989Didier Trono, Mark B. Feinberg +1 more
A number of HIV site-directed Gag mutants did show interference with the production of infectious viral particles from cells in which they were cotransfected with a wild-type proviral DNA.
Journal of VirologyVirions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates
285 Citations1992John P. Moore, Jane A. McKeating +3 more
It is suggested that reduced sCD4 binding and increased gp120 retention together account for the relative resistance of these primary isolates to neutralization by s CD4 and CD4-IgG and that virions of different HIV-1 isolates vary both in the mechanism of sCD 4 binding and in subsequent conformational changes in their envelope glycoproteins.
CellMutational analysis of HIV-1 Tat minimal domain peptides: Identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression
256 Citations1989Maurice Green, Masaho Ishino +1 more
This work postulates that Tat mutant peptides with an inactive region II and a functional region III can behave as dominant negative mutants and synthesizes minimal domain peptides containing single amino substitutions for amino acid residues within region II that are conserved among different HIV isolates.
CellAltered cytoplasmic domains affect intracellular transport of the vesicular stomatitis virus glycoprotein
249 Citations1983John K. Rose, J E Bergmann
Deletion mutants affecting the structure of the cytoplasmic domain fell into two classes and indirect immunofluorescence microscopy suggested that mutant proteins in both classes may accumulate in the rough endoplasmic reticulum.
Journal of VirologyCD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor
228 Citations1990Bruce Crise, Linda Buonocore +1 more
Coexpression of the human immunodeficiency virus type 1 glycoprotein precursor, gp160, and its cellular receptor CD4 in HeLa cells and results showed that newly synthesized CD4 and gp160 form a complex prior to transport from the endoplasmic reticulum (ER).
Proceedings of the National Academy of SciencesHuman immunodeficiency virus-like particles produced by a vaccinia virus expression vector.
215 Citations1989Velissarios Karacostas, Kunio Nagashima +2 more
The production of noninfectious virus-like particles by expression vectors should be useful for biochemical studies and could provide a safe source of material for the development of vaccines.
Journal of VirologyMutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160
173 Citations1989Eric O. Freed, David Myers +1 more
The findings demonstrate that despite its highly conserved nature, the basic pair of amino acids at the site of gp160 cleavage is not absolutely required for proper envelope glycoprotein processing.
The Journal of Experimental MedicineThe human immunodeficiency virus gp120 binding site on CD4: delineation by quantitative equilibrium and kinetic binding studies of mutants in conjunction with a high-resolution CD4 atomic structure.
160 Citations1992Ulrich Moebius, Linda K. Clayton +3 more
The first immunoglobulin V-like domain of CD4 contains the binding site for human immunodeficiency virus gp120; this overlap needs to be considered in the design of inhibitors of the CD4-gp120 interaction.
Journal of VirologyIntracellular interaction of human immunodeficiency virus type 1 (ARV-2) envelope glycoprotein gp160 with CD4 blocks the movement and maturation of CD4 to the plasma membrane
130 Citations1990M.A. Jabbar, Debi P. Nayak
It is demonstrated that a specific intracellular interaction between gp160 and CD4 was responsible for the cell surface down-regulation of CD4 in cells expressing both the envelope glycoprotein of HIV-1 and its receptor, CD4.
NaturePrevention of HIV-1 glycoprotein transport by soluble CD4 retained in the endoplasmic reticulum
108 Citations1990Linda Buonocore, John K. Rose
Journal of VirologyConstruction of recombinant murine retroviruses that express the human T-cell leukemia virus type II and human T-cell lymphotropic virus type III trans activator genes
106 Citations1986C A Rosen, Joseph Sodroski +2 more
Use of these recombinant vectors permits high-efficiency gene transfer into a wide variety of cells, thereby providing the opportunity to study the biochemical effects associated with tat II and tat III gene expression.
Proceedings of the National Academy of SciencesSelective killing of CD4+ cells harboring a human immunodeficiency virus-inducible suicide gene prevents viral spread in an infected cell population.
101 Citations1992Manuel Caruso, David Klatzmann
Exposure to HSV1-TK generates a pool of CD4+ booby-trapped cells that, as a population, are resistant to HIV infection, providing a rationale for the use of suicide genes in the design of gene therapy of HIV infection.
Proceedings of the National Academy of SciencesInhibition of human immunodeficiency virus (HIV) replication by HIV-trans-activated alpha 2-interferon.
96 Citations1989Daniel P. Bednarik, J D Mosca +2 more
The data suggest that virus-trans-activated alpha 2-interferon synthesis can be used as a selective inhibitor of HIV replication.
Journal of VirologyInhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression
87 Citations1991Sadhna Joshi, Allan Van Brunschot +4 more
The results indicate that sense and antisense approaches can be used to interfere with HIV-1 multiplication.
Proceedings of the National Academy of SciencesHuman immunodeficiency virus tat-activated expression of poliovirus protein 2A inhibits mRNA translation.
54 Citations1989Xiaohong Sun, David Baltimore
Protein 2A can, by itself, carry out the inhibition of cellular protein synthesis characteristic of a poliovirus infection and the HIV tat activation provides a very effective method to control gene expression in mammalian cells.