HIV-1 induced AIDS is an allergy and the allergen is the shed gp120 - a review, hypothesis, and implications

被引:21
作者
Becker, Y [1 ]
机构
[1] Hebrew Univ Jerusalem, Fac Med, Dept Mol Virol, IL-91120 Jerusalem, Israel
关键词
AIDS syndrome; endogenous allergens; hematopoietic cells; HIV-1; gp120; IgE/Fc epsilon RI complex; IgE V(H)3 domain; IL-4; cytokine; superantigen domain;
D O I
10.1023/B:VIRU.0000025778.56507.61
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The possibility that the induction of T helper 2 (Th2) cytokine synthesis and the gradual increase in interleukin 4 (IL-4) and IgE levels during HIV-1 infection are an allergic response to HIV-1 proteins was raised in the author's previous article [ Becker, Virus Genes 28, 1-4, 2004]. The present review extends this hypothesis by citing experimental reports which indicate that HIV-1 shed gp120 virions share a striking resemblance with the allergens that bind to IgE molecules bound to Fc epsilon receptor I-positive (FcepsilonRI) cells ( mast cells, basophils, monocytes, and dendritic cells, DC) and then induce them to release and synthesize the IL-4 cytokine. In the earlier review, it was established that the IL-4 cytokine is responsible for the following processes: IgE synthesis by B cells and the inhibition of antiviral IgG synthesis; the inactivation of T helper 1 (Th1) cells; and the inhibition of the antiviral cytotoxic T cell (CTL) response. The binding of the shed gp120 to B cell-bound immunoglobulin (Ig) depletes these cells. Moreover, it was reported that the viral regulatory proteins Tat and Vpr also stimulate IL-4 release from basophils. The mode of action used by HIV-1 gp120 in the induction of IL-4 [ Becker, Virus Genes 28, 1-14, 2004] revealed that the viral protein contains a superantigen (SAg) domain that is capable of binding to the V(H)3 domain of IgE and Ig; namely, the shed gp120 protein act as endogenous and environmental allergens that bind to IgE molecules, which are bound to the FceRI receptors on hematopoietic cells. Based on these findings, it is hypothesized that gp120 is an allergen. Consequently, it can be inferred that the active replication of HIV-1 in infected individuals constantly exposes the immune system to an increase in the allergen content until the host immunity is eventually compromised. These finding suggest that HIV-1 engage in a two-pronged attack of the human immune system: it infects Th2 cells, macrophages, and DCs and then replicates at these venues; and the shed gp120 cells cause an allergy. This allergic condition consequently prevents the induction of Th1 cells, cytokine synthesis, and antiviral CTLs that are needed to clear the infecting virus and thus devitalizes the antivirals that are used to treat the virus infection. It was hypothesized [Becker, Virus Genus 28, 1-14, 2004] that the HIV-1 induced allergy can be treated with IL-4 inhibitors or immune response modifiers. A treatment that employs both antivirals and anti-allergen drugs may very well defeat the AIDS syndrome. Another implication of the present hypothesis is the need to improve the viral antigen used for vaccinating healthy individuals against HIV-1 infection. It is thus suggested harmful domains be eliminated from the gp120.
引用
收藏
页码:319 / 331
页数:13
相关论文
共 62 条
  • [1] Aalberse RC, 2000, J ALLERGY CLIN IMMUN, V106, P228, DOI 10.1067/mai.2000.108434
  • [2] ACQUIRED IMMUNE DYSFUNCTION IN HOMOSEXUAL MEN - IMMUNOLOGICAL PROFILES
    AMMANN, AJ
    ABRAMS, D
    CONANT, M
    CHUDWIN, D
    COWAN, M
    VOLBERDING, P
    LEWIS, B
    CASAVANT, C
    [J]. CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1983, 27 (03): : 315 - 325
  • [3] HIV-1 viral protein R compromises cellular immune function in vivo
    Ayyavoo, V
    Muthumani, K
    Kudchodkar, S
    Zhang, DH
    Ramanathan, P
    Dayes, NS
    Kim, JJ
    Sin, JI
    Montaner, LJ
    Weiner, DB
    [J]. INTERNATIONAL IMMUNOLOGY, 2002, 14 (01) : 13 - 22
  • [4] Molecular mechanisms of immunoglobulin E regulation
    Bacharier, LB
    Jabara, H
    Geha, RS
    [J]. INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 1998, 115 (04) : 257 - 269
  • [5] The changes in the T helper 1 (Th1) and T helper 2 (Th2) cytokine balance during HIV-1 infection are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers - A review and hypothesis
    Becker, Y
    [J]. VIRUS GENES, 2004, 28 (01) : 5 - 18
  • [6] Vaccinia virus pathogenicity in atopic dermatitis is caused by allergen-induced immune response that prevents the antiviral cellular and humoral immunity
    Becker, Y
    [J]. VIRUS GENES, 2003, 27 (03) : 269 - 282
  • [7] BECKER Y, 1996, NOVEL STRATEGIES DES, P97
  • [8] IMMUNOGLOBULIN-V(H)3 GENE-PRODUCTS - NATURAL LIGANDS FOR HIV GP120
    BERBERIAN, L
    GOODGLICK, L
    KIPPS, TJ
    BRAUN, J
    [J]. SCIENCE, 1993, 261 (5128) : 1588 - 1591
  • [9] ANTIBODIES OF HIV-1 POSITIVE SUBJECTS AND EXPERIMENTALLY IMMUNIZED PRIMATES AND RODENTS BIND TO SEQUENCE DIVERGENT REGIONS OF THE 3RD VARIABLE DOMAIN (V3) OF GP120
    BOUDET, F
    GIRARD, M
    THEZE, J
    ZOUALI, M
    [J]. INTERNATIONAL IMMUNOLOGY, 1992, 4 (02) : 283 - 294
  • [10] What establishes a protein as an allergen?
    Bredehorst, R
    David, K
    [J]. JOURNAL OF CHROMATOGRAPHY B, 2001, 756 (1-2): : 33 - 40