INTRODUCTION: HIV viremia is the essential element for progression of an initial HIV infection into AIDS and death. The currently approved management relies primarily on chemotherapy repressing the HIV replication in the infected CD4+ cells, although with severe systemic adverse effects. The problem is that it does not physically eliminate viruses, which then not only keep infecting healthy cells of these patients, but also promote infections of other people. SPECIFIC AIM: An overall objective of our work is biomolecular engineering of virus apheresis tags (VAT) that eliminate viremias without adverse effects. The specific aim of this project was biomolecular engineering of Human Immunodeficiency Virus Apheresis Tags (HIVAT): CD4-Au-Fe3O4, CD4-SiO2-Fe3O4, anti-gp120-Au-Fe3O4, and anti-gp120-SiO2-Fe3O4. HEALTHY DONORS AND PATIENTS: Per the Institutional Review Board's approval and in compliance with Declaration of Helsinki, healthy donors and patients were presented with Patient Bill of Rights and provided Patient Informed Consent, while all the procedures were pursued by the licensed physicians. MATERIALS AND METHODS: CD4, gp120, gp41, gp160, anti-gp120, p24 were transgenomically expressed. Superparamagnetic core-shell particles (SPM-CSP) were synthesized. SPM-CSP were used as the nucleation centers for assembling the expressed molecules upon them to create virus apheresis tags (VAT). VAT were injected into the blood or lymph acquired from the HIV+ and HBV+ patients followed by apheresis at 0.47 - 9.4 T. VAT efficacy in eliminating viremia was determined through immunoblots, NMR and q-RT-PCR. RESULTS: Treatment of blood or lymph of the HIV+ patients' with VAT followed by virus apheresis resulted in rapid elimination of the HIV viremia. Efficacy of apheresis was contingent upon the gravity of viremia versus doses and regimens of VAT. Importantly, administration of VAT also effectively improved levels of non-infected CD4+ lymphocytes. DISCUSSION / CONCLUSIONS: Herein, we present the proof of concept for a new, effective treatment with virus apheresis tags (VAT), specifically Human Immunodeficiency Virus Apheresis Tags (HIVAT), of the HIV+ patients' blood and lymph, which is eliminating the HIV viremia.It can be easily adapted as treatments of viremias perpetrated by other deadly viruses, which we vigorously pursue.
INTRODUCTION: HIV viremia is the essential element for progression of an initial HIV infection into AIDS and death. The currently approved management relies primarily on chemotherapy repressing the HIV replication in the infected CD4+ cells, although with severe systemic adverse effects. The problem is that it does not physically eliminate viruses, which then not only keep infecting healthy cells of these patients, but also promote infections of other people. SPECIFIC AIM: An overall objective of our work is biomolecular engineering of virus apheresis tags (VAT) that eliminate viremias without adverse effects. The specific aim of this project was biomolecular engineering of Human Immunodeficiency Virus Apheresis Tags (HIVAT): CD4-Au-Fe3O4, CD4-SiO2-Fe3O4, anti-gp120-Au-Fe3O4, and anti-gp120-SiO2-Fe3O4. HEALTHY DONORS AND PATIENTS: Per the Institutional Review Board's approval and in compliance with Declaration of Helsinki, healthy donors and patients were presented with Patient Bill of Rights and provided Patient Informed Consent, while all the procedures were pursued by the licensed physicians. MATERIALS AND METHODS: CD4, gp120, gp41, gp160, anti-gp120, p24 were transgenomically expressed. Superparamagnetic core-shell particles (SPM-CSP) were synthesized. SPM-CSP were used as the nucleation centers for assembling the expressed molecules upon them to create virus apheresis tags (VAT). VAT were injected into the blood or lymph acquired from the HIV+ and HBV+ patients followed by apheresis at 0.47 - 9.4 T. VAT efficacy in eliminating viremia was determined through immunoblots, NMR and q-RT-PCR. RESULTS: Treatment of blood or lymph of the HIV+ patients' with VAT followed by virus apheresis resulted in rapid elimination of the HIV viremia. Efficacy of apheresis was contingent upon the gravity of viremia versus doses and regimens of VAT. Importantly, administration of VAT also effectively improved levels of non-infected CD4+ lymphocytes. DISCUSSION / CONCLUSIONS: Herein, we present the proof of concept for a new, effective treatment with virus apheresis tags (VAT), specifically Human Immunodeficiency Virus Apheresis Tags (HIVAT), of the HIV+ patients' blood and lymph, which is eliminating the HIV viremia.It can be easily adapted as treatments of viremias perpetrated by other deadly viruses, which we vigorously pursue.
Entities:
Keywords:
Acquired Immunodeficiency Syndrome (AIDS); CD4+ lymphocyte; Cluster of Differentiation 4 (CD4); Human Immunodeficiency Virus (HIV); Human Immunodeficiency Virus Apheresis Tag (HIVAT); anti-gp120; anti-gp160; anti-gp41; apheresis; glycoprotein 120 (gp120); glycoprotein 160 (gp160); glycoprotein 41 (gp41); superparamagnetic particle (SPM); viremia; virus apheresis tag (VAT)
Authors: James Arthos; Claudia Cicala; Tavis D Steenbeke; Tae-Wook Chun; Charles Dela Cruz; Douglas B Hanback; Prateeti Khazanie; Daniel Nam; Peter Schuck; Sara M Selig; Donald Van Ryk; Margery A Chaikin; Anthony S Fauci Journal: J Biol Chem Date: 2002-01-22 Impact factor: 5.157
Authors: M S Saag; M J Crain; W D Decker; S Campbell-Hill; S Robinson; W E Brown; M Leuther; R J Whitley; B H Hahn; G M Shaw Journal: J Infect Dis Date: 1991-07 Impact factor: 5.226
Authors: S J Clark; M S Saag; W D Decker; S Campbell-Hill; J L Roberson; P J Veldkamp; J C Kappes; B H Hahn; G M Shaw Journal: N Engl J Med Date: 1991-04-04 Impact factor: 91.245
Authors: T L Hodges; J O Kahn; L D Kaplan; J E Groopman; P A Volberding; A J Amman; C J Arri; L M Bouvier; J Mordenti; A E Izu Journal: Antimicrob Agents Chemother Date: 1991-12 Impact factor: 5.191