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IGA MEDIATED DEFENSES AGAINST HIV-1

Wright, Alison Laing
http://rave.ohiolink.edu/etdc/view?acc_num=case1201290332

Abstract Details

2008, Doctor of Philosophy, Case Western Reserve University, Pathology.
Human immunodeficiency virus (HIV-1) is estimated to have newly infected 2.5 million people worldwide in 2007 (UNAIDS 2007) and current treatments only delay the course of this disease. HIV is primarily transmitted through mucosal surfaces and initially propagates in the lamina propria below the polarized epithelial mucosa. IgA, produced in the lamina propria and transcytosed across the mucosal epithelium, is the first line of defense against HIV. This study was initiated to determine if IgA against the more invariant internal HIV proteins are capable of mediating intraepithelial viral neutralization. Polarized primate epithelial cells expressing the polymeric immunoglobulin receptor (pIgR) were transfected with proviral DNA, and IgA was added to the basolateral side. Transcytosing IgA against the HIV proteins Gag and RT significantly inhibited HIV replication in a concentration dependent manner. Consistent with intracellular neutralization, colocalization of the internal proteins and IgA was visualized with confocal microscopy. Thus, at least in the context of infections of polarized epithelia, antibody-mediated neutralization is not necessarily restricted to viral surface antigens. Another potential IgA defense mechanism against HIV is immune excretion, where IgA can bind and form immune complexes in the basolateral compartment (lamina propria) that can be transported and released apically (luminal). IgA against HIV envelope proteins was used to study the ability of polarized epithelial cells to excrete virus from the basolateral to apical surface via pIgR-mediated binding and transport of HIV-IgA immune complexes. Excretion was dependent on IgA concentration and exposure time. Combination of IgA against gp120 and gp41 showed a synergistic increase of excretion. Each IgA antibody demonstrated different levels of excretion ability, which correlated with the ability of the different IgAs to bind HIV and of the immune complexes to bind pIgR. Confocal microscopy showed the intracellular colocalization of HIV proteins and the anti-HIV IgA. Furthermore, two human epithelial cell lines, expressing endogenous pIgR, also demonstrate HIV excretion. IgA has the potential to neutralize HIV conventionally and intracellularly as well as remove virus from the lamina propria and thereby decrease the viral burden. Understanding these IgA-mediated defenses against HIV has the potential to lead to enhanced immunization strategies to eliminate or reduce early HIV infection.
Yung Huang (Advisor)
144 p.
Health Sciences, Immunology
IgA; Immunoglobulin; HIV; Human immunodeficiency virus; Intracellular Neutralization; Viral Excretion; Mucosal; Immunology; Epithelial; polymeric immunoglobulin receptor; pIgR

Recommended Citations

Citations

  • Wright, A. L. (2008). IGA MEDIATED DEFENSES AGAINST HIV-1 [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1201290332

    APA Style (7th edition)

  • Wright, Alison. IGA MEDIATED DEFENSES AGAINST HIV-1. 2008. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1201290332.

    MLA Style (8th edition)

  • Wright, Alison. "IGA MEDIATED DEFENSES AGAINST HIV-1." Doctoral dissertation, Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1201290332

    Chicago Manual of Style (17th edition)

case1201290332
646
© 2008, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.