Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope
Shuzo Matsushita,Marjorie Robert-Guroff,J Rusche,Atsushi Koito,Toshio Hattori,H Hoshino,K Javaherian,Kiyoshi Takatsuki,S Putney +8 more
TLDR
Results localize an epitope of HIV type-specific neutralization and suggest that neutralizing antibodies may be effective in controlling cell-associated, as well as cell-free, virus infection.Abstract:
A monoclonal antibody was produced to the exterior envelope glycoprotein (gp120) of the human T-cell lymphotropic virus (HTLV)-IIIB isolate of the human immunodeficiency virus (HIV). This antibody binds to gp120 of HTLV-IIIB and lymphadenopathy-associated virus type 1 (LAV-1) and to the surface of HTLV-IIIB- and LAV-1-infected cells, neutralizes infection by cell-free virus, and prevents fusion of virus-infected cells. In contrast, it does not bind, or weakly binds, the envelope of four heterologous HIV isolates and does not neutralize heterologous isolates HTLV-IIIRF and HTLV-IIIMN. The antibody-binding site was mapped to a 24-amino-acid segment, using recombinant and synthetic segments of HTLV-IIIB gp120. This site is within a segment of amino acid variability known to contain the major neutralizing epitopes (S. D. Putney, T. J. Matthews, W. G. Robey, D. L. Lynn, M. Robert-Guroff, W. T. Mueller, A. J. Langlois, J. Ghrayeb, S. R. Petteway, K. J. Weinhold, P. J. Fischinger, F. Wong-Staal, R. C. Gallo, and D. P. Bolognesi, Science 234:1392-1395, 1986). These results localize an epitope of HIV type-specific neutralization and suggest that neutralizing antibodies may be effective in controlling cell-associated, as well as cell-free, virus infection.read more
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Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells.
TL;DR: All 24 sites of gp120 are utilized, including 13 that contain complex- type oligosaccharides as the predominant structures, and 11 that contain primarily high mannose-type and/or hybrid-type oligosACcharide structures.
Journal ArticleDOI
Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling.
TL;DR: The functions of a set of well‐characterized ID regions from a diversity of proteins are presented herein to support the possibility that the relationship between amino acid sequence, disordered ensemble and function might be the dominant paradigm for the molecular recognition that serves as the basis for signaling and regulation by protein molecules.
Journal ArticleDOI
Molecular targets for AIDS therapy
TL;DR: In the future, non-nucleoside-type drugs will likely become more important in the experimental therapy of AIDS, and antiretroviral therapy will exert major effects against the morbidity and mortality caused by HIV.
Journal ArticleDOI
Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding.
TL;DR: Results suggest that discontinuous, conserved epitopes proximal to the binding sites for both CD4 and anti-CD4 binding antibodies become better exposed upon CD4 binding and can serve as targets for neutralizing antibodies.
Journal ArticleDOI
Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant.
Gregory Larosa,Joseph P. Davide,Kent J. Weinhold,Waterbury Julie Ann,Albert T. Profy,John A. Lewis,Alphonse J. Langlois,Gordon R. Dreesman,R N Boswell,Phillip P. Shadduck +9 more
TL;DR: The results suggest that HIV vaccine immunogens chosen because of their similarity to the consensus PND sequence and structure are likely to induce antibodies that neutralize a majority of HIV-1 isolates.
References
More filters
Journal ArticleDOI
Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).
Françoise Barré-Sinoussi,J. C. Chermann,Félix A. Rey,Marie-Thérèse Nugeyre,S. Chamaret,Jacqueline Gruest,Charles Dauguet,Claudine Axler-Blin,F. Vézinet-Brun,Christine Rouzioux,Willy Rozenbaum,Luc Montagnier +11 more
TL;DR: From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.
Journal ArticleDOI
The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus
Angus Dalgleish,Peter C. L. Beverley,Paul R. Clapham,Dorothy H. Crawford,Mel Greaves,Robin A. Weiss +5 more
TL;DR: It is concluded that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS.
Journal ArticleDOI
Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS
TL;DR: 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.
Journal ArticleDOI
Complete nucleotide sequence of the AIDS virus, HTLV-III
Lee Ratner,William A. Haseltine,Roberto Patarca,Kenneth J. Livak,Bruno Starcich,Steven F. Josephs,Ellen R. Doran,J. Antoni Rafalski,Erik A. Whitehorn,Kirk Baumeister,Lucinda A. Ivanoff,Stephen R. Petteway,Mark L. Pearson,James A. Lautenberger,Takis S. Papas,John Ghrayeb,Nancy T. Chang,Robert C. Gallo,Flossie Wong-Staal +18 more
TL;DR: The complete nucleotide sequence of two human T-cell leukaemia type III (HTLV-III) proviral DNAs each have four long open reading frames, the first two corresponding to the gag and pol genes.
Journal ArticleDOI
Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1
Mark Kowalski,Joseph Potz,Ladan Basiripour,Tatyana Dorfman,Wei Chun Goh,Ernest Terwilliger,Andrew Dayton,Craig A. Rosen,William A. Haseltine,Joseph Sodroski +9 more
TL;DR: These findings provide a functional model of the HIV envelope glycoprotein that can be divided into five groups: those that decrease the binding of the envelope protein to the CD4 molecule, those that prevent a post-binding fusion reaction, and those that disrupt the anchorage of the envelopes in the membrane.